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Ma, Xiaofeng, and Nobuo Suga. "Augmentation of Plasticity of the Central Auditory System by the Basal Forebrain and/or Somatosensory Cortex." Journal of Neurophysiology 89, no. 1 (January 1, 2003): 90–103. http://dx.doi.org/10.1152/jn.00968.2001.
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Auditory conditioning (associative learning) or focal electric stimulation of the primary auditory cortex (AC) evokes reorganization (plasticity) of the cochleotopic (frequency) map of the inferior colliculus (IC) as well as that of the AC. The reorganization results from shifts in the best frequencies (BFs) and frequency-tuning curves of single neurons. Since the importance of the cholinergic basal forebrain for cortical plasticity and the importance of the somatosensory cortex and the corticofugal auditory system for collicular and cortical plasticity have been demonstrated, Gao and Suga proposed a hypothesis that states that the AC and corticofugal system play an important role in evoking auditory collicular and cortical plasticity and that auditory and somatosensory signals from the cerebral cortex to the basal forebrain play an important role in augmenting collicular and cortical plasticity. To test their hypothesis, we studied whether the amount and the duration of plasticity of both collicular and cortical neurons evoked by electric stimulation of the AC or by acoustic stimulation were increased by electric stimulation of the basal forebrain and/or the somatosensory cortex. In adult big brown bats ( Eptesicus fuscus), we made the following major findings. 1) Collicular and cortical plasticity evoked by electric stimulation of the AC is augmented by electric stimulation of the basal forebrain. The amount of augmentation is larger for cortical plasticity than for collicular plasticity. 2) Collicular and cortical plasticity evoked by AC stimulation is augmented by somatosensory cortical stimulation mimicking fear conditioning. The amount of augmentation is larger for cortical plasticity than for collicular plasticity. 3) Collicular and cortical plasticity evoked by both AC and basal forebrain stimulations is further augmented by somatosensory cortical stimulation. 4) A lesion of the basal forebrain tends to reduce collicular and cortical plasticity evoked by AC stimulation. The reduction is small and statistically insignificant for collicular plasticity but significant for cortical plasticity. 5) The lesion of the basal forebrain eliminates the augmentation of collicular and cortical plasticity that otherwise would be evoked by somatosensory cortical stimulation. 6) Collicular and cortical plasticity evoked by repetitive acoustic stimuli is augmented by basal forebrain and/or somatosensory cortical stimulation. However, the lesion of the basal forebrain eliminates the augmentation of collicular and cortical plasticity that otherwise would be evoked by somatosensory cortical stimulation. These findings support the hypothesis proposed by Gao and Suga.
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KNISLEY, STEPHEN B. "Exploring Cardiac Response to AC Stimulation." Journal of Cardiovascular Electrophysiology 12, no. 10 (October 2001): 1185–86. http://dx.doi.org/10.1046/j.1540-8167.2001.01185.x.
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Su, Chen-Ying, Tzan Fang, and Hsu-Wei Fang. "Effects of Electrostatic Field on Osteoblast Cells for Bone Regeneration Applications." BioMed Research International 2017 (2017): 1–9. http://dx.doi.org/10.1155/2017/7124817.
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Many external stimulations have been shown to promote bone regeneration. The effects of an alternating current (AC) electrostatic field, one of external stimulations, generated from a device with high voltage and low current output on human osteoblastic cell line have been investigated in this study. We investigated how human osteoblasts responded to an AC electrostatic field, and the output parameters were set as 1 kV and 160 μA. Our results showed that, under such condition, the AC electrostatic field had a downregulation effect on the production ability of alkaline phosphatase and type 1 collagen expression. However, the expression of osteocalcin gene was elevated on the end of EFID treatment suggesting that AC electrostatic field might be a potential stimulation for accelerating the differentiation of osteoblastic cells.
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Ma, Xiaofeng, and Nobuo Suga. "Plasticity of Bat's Central Auditory System Evoked by Focal Electric Stimulation of Auditory and/or Somatosensory Cortices." Journal of Neurophysiology 85, no. 3 (March 1, 2001): 1078–87. http://dx.doi.org/10.1152/jn.2001.85.3.1078.
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Recent findings indicate that the corticofugal system would play an important role in cortical plasticity as well as collicular plasticity. To understand the role of the corticofugal system in plasticity, therefore, we studied the amount and the time course of plasticity in the inferior colliculus (IC) and auditory cortex (AC) evoked by focal electrical stimulation of the AC and also the effect of electrical stimulation of the somatosensory cortex on the plasticity evoked by the stimulation of the AC. In adult big brown bats ( Eptesicus fuscus), we made the following major findings. 1) Electric stimulation of the AC evokes best frequency (BF) shifts, i.e., shifts in frequency-response curves of collicular and cortical neurons. These BF shifts start to occur within 2 min, reach a maximum (or plateau) at 30 min, and then recover ∼180 min after a 30-min-long stimulus session. When the stimulus session is lengthened from 30 to 90 min, the plateau lasts ∼60 min, but BF shifts recover ∼180 min after the session. 2) The electric stimulation of the somatosensory cortex delivered immediately after that of the AC, as in fear conditioning, evokes a dramatic lengthening of the recovery period of the cortical BF shifts but not that of the collicular BF shift. The electric stimulation of the somatosensory cortex delivered before that of the AC, as in backward conditioning, has no effect on the collicular and cortical BF shifts. 3) Electric stimulation of the AC evokes BF shifts not only in the ipsilateral IC and AC but also in the contralateral IC and AC. BF shifts are smaller in amount and shorter in recovery time for contralateral collicular and cortical neurons than for ipsilateral ones. Our findings support the hypothesis that the AC and the corticofugal system have an intrinsic mechanism for reorganization of the IC and AC, that the reorganization is highly specific to a value of an acoustic parameter (frequency), and that the reorganization is augmented by excitation of nonauditory sensory cortex that makes the acoustic stimulus behaviorally relevant to the animal through associative learning.
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Chaudhry, A., and J. G. Granneman. "Effect of hypothyroidism on adenylyl cyclase activity and subtype gene expression in brown adipose tissue." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 273, no. 2 (August 1, 1997): R762—R767. http://dx.doi.org/10.1152/ajpregu.1997.273.2.r762.
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Brown adipose tissue (BAT) expresses several adenylyl cyclase (AC) subtypes, and adrenergic stimulation selectively upregulates AC-III gene expression. Previous studies have described synergistic interactions between the sympathetic nervous system (SNS) and 3,5,3'-triiodothyronine (T3) on the regulation of gene expression in BAT. Because adrenergic stimulation also increases the activity of BAT type II thyroxine 5'-deiodinase (DII) and local T3 generation is important for many functional responses in BAT, we examined the effects of thyroid hormone status on the expression of various AC subtypes. Hypothyroidism selectively increased AC-III mRNA levels in BAT but not in white adipose tissue. Of the other subtypes examined, hypothyroidism did not alter AC-VI mRNA levels and slightly reduced AC-IX mRNA levels in BAT. The increase in AC-III expression was paralleled by an increase in forskolin-stimulated AC activity in BAT membranes. Sympathetic denervation of BAT abolished the increase in both AC activity and AC-III mRNA expression produced by hypothyroidism, but did not affect the expression of other subtypes. Surgical denervation also prevented the induction of AC-III in the cold-stressed euthyroid rat, but injections of T3 failed to alter AC-III expression in intact or denervated BAT. Our results indicate that T3 does not directly affect expression of AC-III. Rather, hypothyroidism increases BAT AC-III expression indirectly via an increase in sympathetic stimulation. Furthermore, our results strongly indicate that the increase in AC activity in hypothyroid BAT is due to increased expression of AC-III.
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Ward, Alex R. "Electrical Stimulation Using Kilohertz-Frequency Alternating Current." Physical Therapy 89, no. 2 (February 1, 2009): 181–90. http://dx.doi.org/10.2522/ptj.20080060.
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Transcutaneous electrical stimulation using kilohertz-frequency alternating current (AC) became popular in the 1950s with the introduction of “interferential currents,” promoted as a means of producing depth-efficient stimulation of nerve and muscle. Later, “Russian current” was adopted as a means of muscle strengthening. This article reviews some clinically relevant, laboratory-based studies that offer an insight into the mechanism of action of kilohertz-frequency AC. It provides some answers to the question: “What are the optimal stimulus parameters for eliciting forceful, yet comfortable, electrically induced muscle contractions?” It is concluded that the stimulation parameters commonly used clinically (Russian and interferential currents) are suboptimal for achieving their stated goals and that greater benefit would be obtained using short-duration (2–4 millisecond), rectangular bursts of kilohertz-frequency AC with a frequency chosen to maximize the desired outcome.
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Raymaekers, S., Z. Van Duppen, K. Demyttenaere, L. Luyten, L. Gabriels, B. Nuttin, and C. Bervoets. "Deep brain stimulation and anterior capsulotomy: The question of autonomy." European Psychiatry 41, S1 (April 2017): S323. http://dx.doi.org/10.1016/j.eurpsy.2017.02.249.
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IntroductionIn carefully selected treatment-refractory patients with obsessive compulsive disorder (OCD), deep brain stimulation (DBS) or anterior capsulotomy (AC) might be considered as a possible treatment. However, the direct intervention in the brain can raise questions about autonomy. Do patients still feel like they are in control of their actions when their behavior is changed by a surgical intervention?Objective/aimsTo examine in both AC and DBS patients whether these intervention influenced perception of autonomy. We aimed to discover any differences in these perceptions when comparing AC and DBS patients.MethodsWe conducted semi-structured interviews with AC and DBS patients. Interviews were recorded digitally and transcribed verbatim. We analyzed interviews in an iterative process based on grounded theory principles.ResultsWe interviewed 10 DBS patients and 6 AC patients. Sense of agency (the awareness that one is the author of his/her own actions) did not seem to be diminished by AC or DBS. However, especially DBS patients are aware of their dependency on a device for their well-being. Another important theme is authenticity (in how far patients perceive their actions and thoughts as matching their self-concept). Feelings of authenticity can be disturbed especially in cases of induced hypomania (for DBS) or apathy (for AC). OCD itself also has an impact on autonomy as patients describe a lack of freedom due to their disorder.ConclusionDespite extensive changes in emotions, behavior and even personal identity after DBS or AC surgery, perceived autonomy was not greatly altered in these OCD patients.Disclosure of interestMedtronic provided grants for research, education, and traveling to B. Nuttin and L. Gabriëls, who hold the Medtronic Chair for Stereotactic Neurosurgery in Psychiatric Disorders at KU Leuven. S. Raymaekers is supported by this Chair. B. Nuttin co-owns a patent on DBS in OCD.
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Ma, Xiaofeng, and Nobuo Suga. "Lateral Inhibition for Center-Surround Reorganization of the Frequency Map of Bat Auditory Cortex." Journal of Neurophysiology 92, no. 6 (December 2004): 3192–99. http://dx.doi.org/10.1152/jn.00301.2004.
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Repetitive acoustic stimulation, auditory fear conditioning, and focal electric stimulation of the auditory cortex (AC) each evoke the reorganization of the central auditory system. Our current study of the big brown bat indicates that focal electric stimulation of the AC evokes center-surround reorganization of the frequency map of the AC. In the center, the neuron's best frequencies (BFs), together with their frequency–tuning curves, shift toward the BFs of electrically stimulated cortical neurons (centripetal BF shifts). In the surround, BFs shift away from the stimulated cortical BF (centrifugal BF shifts). Centripetal BF shifts are much larger than centrifugal BF shifts. An antagonist (bicuculline methiodide) of inhibitory synaptic transmitter receptors changes centrifugal BF shifts into centripetal BF shifts, whereas its agonist (muscimol) changes centripetal BF shifts into centrifugal BF shifts. This reorganization of the AC thus depends on a balance between facilitation and inhibition evoked by focal cortical electric stimulation. Unlike neurons in the AC of the big brown bat, neurons in the Doppler-shifted constant-frequency (DSCF) area of the AC of the mustached bat are highly specialized for fine-frequency analysis and show almost exclusively centrifugal BF shifts for focal electric stimulation of the DSCF area. Our current data indicate that in the highly specialized area, lateral inhibition is strong compared with the less-specialized area and that the specialized and nonspecialized areas both share the same inhibitory mechanism for centrifugal BF shifts.
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Kiritsy, Michael. "Burst Stimulation Could Be the Next Generation of Spinal Cord Stimulation." Topics in Pain Management 31, no. 11 (June 2016): 8–9. http://dx.doi.org/10.1097/01.tpm.0000484123.86649.ac.
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Surikova, Ekaterina Igorevna, Elena Frantsiyants, Irina A. Goroshinskaya, Yulia A. Pogorelova, Valeria A. Bandovkina, Irina Valerevna Neskubina, Andrey A. Maslov, et al. "Does signet-ring cell carcinoma of the stomach (SRCC) need stimulation of neoangiogenesis?" Journal of Clinical Oncology 36, no. 4_suppl (February 1, 2018): 33. http://dx.doi.org/10.1200/jco.2018.36.4_suppl.33.
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33 Background: Tumor neoangiogenesis is a complex coordinated process involving various regulatory molecules. Vascular endothelial growth factors, in particular VEGF-A, are important effectors. A multipotent TGF-β1 cytokine can modulate stromal angiogenesis reactions promoting the tumor growth. Our purpose was to study the function of the system of pro-angiogenic cytokines in tissues of stomach tumors of various histological types - adenocarcinoma (AC) and signet-ring cell carcinoma (SRCC). Methods: The concentrations of VEGF-A, VEGF-R1 and TGF-β1 were studied by ELISA in tumors, peritumoral zone and resection line tissues of gastric cancer patients without preoperative therapy: 15 patients with AC (T2-4N0-2M0, G2-G3, 50-84 years) and 10 patients with SRCC, comparable by sex, age and prevalence of cancer process. Results: Levels of VEGF-A, VEGF-R1 and TGF-β1 in the resection line tissues of AC and SRCC did not differ significantly. VEGF-A in AC tumor tissues exceeded significantly the levels in the resection line (by 2.3 times) and in the peritumoral zone (by 1.8 times). VEGF-A in SRCC tumor tissue did not differ significantly from the levels in the corresponding tissues of the resection line and peritumoral zone, but it was 2.6 times lower than in AC tumor tissues. VEGF-R1 levels in AC and SRCC were similar. TGF-β1 in AC tumor tissues was 3.2 and 2.6 times higher than in the resection line and peritumoral zone, respectively. TGF-β1 in SRCC tumor tissues did not differ from the levels in the peritumoral zone and in healthy tissues; TGF-β1 in tumor tissues was 3.2 times lower in SRCC than in AC. Conclusions: SRCC tumor tissues have significantly lower levels of pro-angiogenic VEGF-А and TGF-β1 cytokines, compared to AC tissues, which can indicate that SRCC has no need to form its own vasculature. It is probably associated with the biological characteristic of this histotype of gastric cancer - diffuse growth pattern, in contrast to the solid structure of AC.
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Cohen, Jonathan E., Chiadi U. Onyike, Virginia L. McElroy, Allison H. Lin, and Thomas W. Abrams. "Pharmacological Characterization of an Adenylyl Cyclase-Coupled 5-HT Receptor in Aplysia: Comparison With Mammalian 5-HT Receptors." Journal of Neurophysiology 89, no. 3 (March 1, 2003): 1440–55. http://dx.doi.org/10.1152/jn.01004.2002.
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We attempted to identify compounds that are effective in blocking the serotonin (5-hydroxytryptamine, 5-HT) receptor(s) that activate adenylyl cyclase (AC) in Aplysia CNS. We call this class of receptor 5-HTapAC. Eight of the 14 antagonists tested were effective against 5-HTapAC in CNS membranes with the following rank order of potency: methiothepin > metergoline ∼ fluphenazine > clozapine > cyproheptadine ∼ risperidone ∼ ritanserin > NAN-190. GR-113808, olanzapine, Ro-04-6790, RS-102221, SB-204070, and spiperone were inactive. Methiothepin completely blocked 5-HT stimulation of AC with a K b of 18 nM. Comparison of the pharmacological profile of the 5-HTapAC receptor with those of mammalian 5-HT receptor subtypes suggested it most closely resembles the 5-HT6 receptor. AC stimulation in Aplysia sensory neuron (SN) membranes was also blocked by methiothepin. Methiothepin substantially inhibited two effects of 5-HT on SN firing properties that are mediated by a cAMP-dependent reduction in S-K+ current: spike broadening in tetraethylammonium/nifedipine and increased excitability. Consistent with cyproheptadine blocking 5-HT stimulation of AC, cyproheptadine also blocked the 5-HT-induced increase in SN excitability. Methiothepin was less effective in blocking AC-mediated modulatory effects of 5-HT in electrophysiological experiments on SNs than in blocking AC stimulation in CNS or SN membranes. This reduction in potency appears to be due to effects of the high ionic strength of physiological saline on the binding of this antagonist to the receptor. Methiothepin also antagonized AC-coupled dopamine receptors but not AC-coupled small cardioactive peptide receptors. In conjunction with other pharmacological probes, this antagonist should be useful in analyzing the role of 5-HT in various forms of neuromodulation in Aplysia.
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Sridharan, Arati, Sanchit Chirania, Bruce Towe, and Jit Muthuswamy. "Remote Stimulation of Sciatic Nerve Using Cuff Electrodes and Implanted Diodes." Micromachines 9, no. 11 (November 14, 2018): 595. http://dx.doi.org/10.3390/mi9110595.
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We demonstrate a method of neurostimulation using implanted, free-floating, inter-neural diodes. They are activated by volume-conducted, high frequency, alternating current (AC) fields and address the issue of instability caused by interconnect wires in chronic nerve stimulation. The aim of this study is to optimize the set of AC electrical parameters and the diode features to achieve wireless neurostimulation. Three different packaged Schottky diodes (1.5 mm, 500 µm and 220 µm feature sizes) were tested in vivo (n = 17 rats). A careful assessment of sciatic nerve activation as a function of diode–dipole lengths and relative position of the diode was conducted. Subsequently, free-floating Schottky microdiodes were implanted in the nerve (n = 3 rats) and stimulated wirelessly. Thresholds for muscle twitch responses increased non-linearly with frequency. Currents through implanted diodes within the nerve suffer large attenuations (~100 fold) requiring 1–2 mA drive currents for thresholds at 17 µA. The muscle recruitment response using electromyograms (EMGs) is intrinsically steep for subepineurial implants and becomes steeper as diode is implanted at increasing depths away from external AC stimulating electrodes. The study demonstrates the feasibility of activating remote, untethered, implanted microscale diodes using external AC fields and achieving neurostimulation.
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Li, Ying, Chao Sun, Jiujie Kuang, Changchun Ji, and Jiangtao Wu. "The Effect of Moxibustion Stimulation on Local and Distal Skin Temperature in Healthy Subjects." Evidence-Based Complementary and Alternative Medicine 2019 (April 2, 2019): 1–10. http://dx.doi.org/10.1155/2019/3185987.
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The aim of this study is to investigate the response of local and distal skin temperature to moxibustion stimulation (MS) and explore the effects of MS on sympathetic nerve activity. The distal skin temperatures of fingertips, as an indicator for sympathetic reflex response, were recorded using infrared camera during resting period (10 min), MS period (10 min), and natural cooling period (15 min), respectively. The MS without ash cleaning (AC) was applied to acupoints Quze (PC3) (Group I) and Lao Gong (PC8) (Group II), respectively. In Group III, the MS with the operation of AC was performed on PC8. The temperature responses of the local stimulation points and corresponding control points were also investigated. At the beginning of MS period, a significant increase of temperature on the stimulation point accompanied by a simultaneous reduction of temperature on fingertips was observed. A marked negative correlation was also obtained between temperature changes in the stimulation point and in the fingertips. At the end of natural cooling period (t = 34 min), the temperature of stimulation point was obviously higher than baseline values. In contrast, the temperatures of fingertips increased and then returned to the baseline levels during the second minute of MS period. In Group III, the temperature of stimulation point increased every time with the operation of AC, accompanied by the temperature decrease of middle fingertip. The findings suggest that moxibustion may trigger the sympathetic nervous system and induce the reduction of microcirculation, accompanied by a reduction of fingertip temperature. In addition, the operation of AC caused repeated cycles of thermal stimulation on the stimulation point, which may repetitively activate cutaneous sympathetic nerve fibres and evoke the temperature reduction of fingertips.
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Su, Tzu-Rong, Wen-Shan Zei, Ching-Chyuan Su, George Hsiao, and Min-Jon Lin. "The Effects of the KCNQ Openers Retigabine and Flupirtine on Myotonia in Mammalian Skeletal Muscle Induced by a Chloride Channel Blocker." Evidence-Based Complementary and Alternative Medicine 2012 (2012): 1–9. http://dx.doi.org/10.1155/2012/803082.
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The purpose of this study was to investigate the effect of KCNQ (potassium channel, voltage-gated, KQT-like subfamily) openers in preventing myotonia caused by anthracene-9-carboxylic acid (9-AC, a chloride channel blocker). An animal model of myotonia can be elicited in murine skeletal muscle by 9-AC treatment. KCNQ openers, such as retigabine and flupirtine, can inhibit the increased twitch amplitude (0.1 Hz stimulation) and reduce the tetanic fade (20 Hz stimulations) observed in the presence of 9-AC. Furthermore, the prolonged twitch duration of skeletal muscle was also inhibited by retigabine or flupirtine. Lamotrigine (an anticonvulsant drug) has a lesser effect on the muscle twitch amplitude, tetanic fade, and prolonged twitch duration as compared with KCNQ openers. In experiments using intracellular recordings, retigabine and flupirtine clearly reduced the firing frequencies of repetitive action potentials induced by 9-AC. These data suggested that KCNQ openers prevent the myotonia induced by 9-AC, at least partly through enhancing potassium conductance in skeletal muscle. Taken together, these results indicate that KCNQ openers are potential alternative therapeutic agents for the treatment of myotonia.
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Parenti, M., D. Cocchi, G. Ceresoli, C. Marcozzi, and E. E. Müller. "Age-related changes of growth hormone secretory mechanisms in the rat pituitary gland." Journal of Endocrinology 131, no. 2 (November 1991): 251–57. http://dx.doi.org/10.1677/joe.0.1310251.
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ABSTRACT The mechanisms underlying the age-related decrease and increase in somatotroph responsiveness to growth hormone-releasing factor (GHRF) and somatostatin respectively were studied in rat pituitary membranes in vitro. Basal adenylate cyclase (AC) activity was similar in pituitary membranes from rats of 8 days (either sex) and male rats of 3 months, but it was almost threefold higher in membranes from male rats of 21–23 months. GHRF induced a lower percentage stimulation of AC activity in membranes from infant and old than adult rats. Somatostatin inhibited stimulation of AC induced by forskolin more effectively in membranes from adult than infant and old rats. In parallel experiments, since the tissue we used is formed by a mixed population of pituitary cells, we evaluated, for comparison, the effect on AC of neurohormones, i.e. vasoactive intestinal polypeptide (VIP) and dopamine which act primarily on lactotrophs. VIP induced a lower fold-stimulation of AC activity in membranes from infant and old than adult rats. Dopamine inhibited forskolin-induced stimulation of AC in the following rank order of magnitude: old, adult and infant rats, and was also more effective in inhibiting basal AC activity in old than in adult rats. The stimulatory and inhibitory G proteins (Gs and Gi) coupled to AC were measured indirectly by evaluating stimulatory and inhibitory effects of different concentrations of GTP on AC. GTP, at stimulatory concentrations, increased AC activity in membranes from infant and adult rats similarly whereas its effect was significantly greater in membranes from old rats. Conversely, GTP, at inhibitory concentrations, decreased AC activity similarly in membranes from adult and infant rats, whereas in old rats inhibition was apparent at more than a tenfold lower concentration of GTP. These data suggest (1) that the greater somatotroph sensitivity to GHRF in terms of GH secretion of the early postnatal period is not due to supersensitive GHRF receptors but rather may be accounted for, at least partially, by the low function of somatostatinergic receptors; (2) that the inability of GHRF to stimulate GH release in aged rats probably results from an uncoupling between the GHRF receptor and the G protein; and (3) that in aged rats the decreased ability of somatostatin to inhibit AC activity, in spite of the high Gi activity, results from a reduced number of somatotroph cells and, hence, receptors. Journal of Endocrinology (1991) 131, 251–257
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Frings, S. "Protein kinase C sensitizes olfactory adenylate cyclase." Journal of General Physiology 101, no. 2 (February 1, 1993): 183–205. http://dx.doi.org/10.1085/jgp.101.2.183.
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Effects of neurotransmitters on cAMP-mediated signal transduction in frog olfactory receptor cells (ORCs) were studied using in situ spike recordings and radioimmunoassays. Carbachol, applied to the mucosal side of olfactory epithelium, amplified the electrical response of ORCs to cAMP-generating odorants, but did not affect unstimulated cells. A similar augmentation of odorant response was observed in the presence of phorbol dibutyrate (PDBu), an activator of protein kinase C (PKC). The electrical response to forskolin, an activator of adenylate cyclase (AC), was also enhanced by PDBu, and it was attenuated by the PKC inhibitor Goe 6983. Forskolin-induced accumulation of cAMP in olfactory tissue was potentiated by carbachol, serotonin, and PDBu to a similar extent. Potentiation was completely suppressed by the PKC inhibitors Goe 6983, staurosporine, and polymyxin B, suggesting that the sensitivity of olfactory AC to stimulation by odorants and forskolin was increased by PKC. Experiments with deciliated olfactory tissue indicated that sensitization of AC was restricted to sensory cilia of ORCs. To study the effects of cell Ca2+ on these mechanisms, the intracellular Ca2+ concentration of olfactory tissue was either increased by ionomycin or decreased by BAPTA/AM. Increasing cell Ca2+ had two effects on cAMP production: (a) the basal cAMP production was enhanced by a mechanism sensitive to inhibitors of calmodulin; and (b) similar to phorbol ester, cell Ca2+ caused sensitization of AC to stimulation by forskolin, an effect sensitive to Goe 6983. Decreasing cell Ca2+ below basal levels rendered AC unresponsive to stimulation by forskolin. These data suggest that a crosstalk mechanism is functional in frog ORCs, linking the sensitivity of AC to the activity of PKC. At increased activity of PKC, olfactory AC becomes more responsive to stimulation by odorants, forskolin, and cell Ca2+. Neurotransmitters appear to use this crosstalk mechanism to regulate olfactory sensitivity.
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Shen, Jia X., and Dermot M. F. Cooper. "AKAP79, PKC, PKA and PDE4 participate in a Gq-linked muscarinic receptor and adenylate cyclase 2 cAMP signalling complex." Biochemical Journal 455, no. 1 (September 13, 2013): 47–56. http://dx.doi.org/10.1042/bj20130359.
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This study shows that a key signalling molecule, AC (adenylate cyclase), binds a scaffolding molecule (AKAP) which a kinase recruits which can modulate AC activity in response to stimulation of a non-canonical signalling cascade.
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Tsigaridas, Nikolaos, Katerina Naka, Panagiotis Tsapogas, Eleft Herios Pelechas, and Dimitrios Damigos. "Spinal cord stimulation in refractory angina. A systematic review of randomized controlled trials." Acta Cardiologica 70, no. 2 (April 2015): 233–43. http://dx.doi.org/10.1080/ac.70.2.3073516.
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Durr, Jacques A., Johannes Hensen, Tobias Ehnis, and Mary S. Blankenship. "Chlorpropamide upregulates antidiuretic hormone receptors and unmasks constitutive receptor signaling." American Journal of Physiology-Renal Physiology 278, no. 5 (May 1, 2000): F799—F808. http://dx.doi.org/10.1152/ajprenal.2000.278.5.f799.
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The mechanism by which chlorpropamide (CP) treatment promotes antidiuresis is unknown. CP competitively inhibited antidiuretic hormone (ADH) binding and adenylyl cyclase (AC) stimulation (inhibition constants K i and K′i of 2.8 mM and 250 μM, respectively) in the LLC-PK1 cell line. CP (333 μM) increased the apparent K a of ADH for AC activation (0.31 vs. 0.08 nM) without affecting a maximal response, suggesting competitive antagonism. Because CP lowers “basal” AC activity and the AC activation-ADH receptor occupancy relationship (A-O plots), it is an ADH inverse agonist. Twenty-four-hour CP exposure (100 μM) upregulated the ADH receptors without affecting affinity. This lowered K a and increased basal AC activity and maximal response (1.86 vs. 1.35 and 14.9 vs. 10.6 fmol cAMP ⋅ min− 1 ⋅ 103cells− 1, n = 6, P < 0.05). NaCl, which potentiates ADH stimulation, also increased basal AC activity. This, together with the CP-ADH inverse agonism and increased basal AC activity at higher receptor density, unmasks constitutive receptor signaling. The CP-ADH inverse agonism explains receptor upregulation and predicts the need for residual ADH with functional isoreceptors for CP-mediated antidiuresis. This could be why CP ameliorates partial central diabetes insipidus but not nephrogenic diabetes insipidus.
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Shen, T., Y. Suzuki, M. Poyard, N. Miyamoto, N. Defer, and J. Hanoune. "Expression of adenylyl cyclase mRNAs in the adult, in developing, and in the Brattleboro rat kidney." American Journal of Physiology-Cell Physiology 273, no. 1 (July 1, 1997): C323—C330. http://dx.doi.org/10.1152/ajpcell.1997.273.1.c323.
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The activity and expression of adenylyl cyclases (AC) were examined in the adult rat renal cortex and medulla. Northern blot analysis and in situ hybridization demonstrated that AC-6 was the predominant isoform in the adult rat kidney, whereas AC-4, -5, and -9 had a lower expression. AC-4 expression was higher in the cortex, and AC-5 and AC-6 were higher in the medulla. AC-9 expression was at the same level in both regions. AC activity was high in the fetus and declined in the adult. At all stages, AC activity was sensitive to parathyroid hormone, whereas no stimulation by vasopressin and isoproterenol was found in the fetus and the neonate. AC-5 and AC-6 mRNAs increased at day 1 and then markedly decreased, paralleling the decline in AC activity. The mRNA of AC-4 did not change and that of AC-9 increased markedly until adult. In the homozygous Brattleboro rat kidney, the expression of all these isoforms was decreased.
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Pepper, Joshua, Marwan Hariz, and Ludvic Zrinzo. "Deep brain stimulation versus anterior capsulotomy for obsessive-compulsive disorder: a review of the literature." Journal of Neurosurgery 122, no. 5 (May 2015): 1028–37. http://dx.doi.org/10.3171/2014.11.jns132618.
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Obsessive-compulsive disorder (OCD) is a chronic and debilitating psychiatric condition. Traditionally, anterior capsulotomy (AC) was an established procedure for treatment of patients with refractory OCD. Over recent decades, deep brain stimulation (DBS) has gained popularity. In this paper the authors review the published literature and compare the outcome of AC and DBS targeting of the area of the ventral capsule/ventral striatum (VC/VS) and nucleus accumbens (NAcc). Patients in published cases were grouped according to whether they received AC or DBS and according to their preoperative scores on the Yale-Brown Obsessive-Compulsive Scale (YBOCS), and then separated according to outcome measures: remission (YBOCS score < 8); response (≥ 35% improvement in YBOCS score); nonresponse (< 35% improvement in YBOCS score); and unfavorable (i.e., worsening of the baseline YBOCS score). Twenty studies were identified reporting on 170 patients; 62 patients underwent DBS of the VC/VS or the NAcc (mean age 38 years, follow-up 19 months, baseline YBOCS score of 33), and 108 patients underwent AC (mean age 36 years, follow-up 61 months, baseline YBOCS score of 30). In patients treated with DBS there was a 40% decrease in YBOCS score, compared with a 51% decrease for those who underwent AC (p = 0.004). Patients who underwent AC were 9% more likely to go into remission than patients treated with DBS (p = 0.02). No difference in complication rates was noted. Anterior capsulotomy is an efficient procedure for refractory OCD. Deep brain stimulation in the VC/VS and NAcc area is an emerging and promising therapy. The current popularity of DBS over ablative surgery for OCD is not due to nonefficacy of AC, but possibly because DBS is perceived as more acceptable by clinicians and patients.
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Ronen, Ofri, Miriam Geal-Dor, Michal Kaufmann-Yehezkely, Ronen Perez, Shai Chordekar, Cahtia Adelman, and Haim Sohmer. "Inner Ear Excitation in Normal and Postmastoidectomy Participants by Fluid Stimulation in the Absence of Air- and Bone-Conduction Mechanisms." Journal of the American Academy of Audiology 28, no. 02 (February 2017): 152–60. http://dx.doi.org/10.3766/jaaa.16036.
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Background: Hearing can be induced not only by airborne sounds (air conduction [AC]) and by the induction of skull vibrations by a bone vibrator (osseous bone conduction [BC]), but also by inducing vibrations of the soft tissues of the head, neck, and thorax. This hearing mode is called soft tissue conduction (STC) or nonosseous BC. Purpose: This study was designed to gain insight into the mechanism of STC auditory stimulation. Research Design: Fluid was applied to the external auditory canal in normal participants and to the mastoidectomy common cavity in post–radical mastoidectomy patients. A rod coupled to a clinical bone vibrator, immersed in the fluid, delivered auditory frequency vibratory stimuli to the fluid. The stimulating rod was in contact with the fluid only. Thresholds were assessed in response to the fluid stimulation. Study Sample: Eight ears in eight normal participants and eight ears in seven post–radical mastoidectomy patients were studied. Data Collection and Analysis: Thresholds to AC, BC, and fluid stimulation were assessed. The postmastoidectomy patients were older than the normal participants, with underlying sensorineural hearing loss (SNHL). Therefore, the thresholds to the fluid stimulation in each participant were corrected by subtracting his BC threshold, which expresses any underlying SNHL. Results: Hearing thresholds were obtained in each participant, in both groups in response to the fluid stimulation at 1.0 and 2.0 kHz. The fluid thresholds, corrected by subtracting the BC thresholds, did not differ between the groups at 1.0 kHz. However, at 2.0 kHz the corrected fluid thresholds in the mastoidectomy patients were 10 dB lower (better) than in the normal participants. Conclusions: Since the corrected fluid thresholds at 1.0 kHz did not differ between the groups, the response to fluid stimulation in the normal participants at least at 1.0 kHz was probably not due to vibrations of the tympanic membrane and of the ossicular chain induced by the fluid stimulation, since these structures were absent in the mastoidectomy patients. In addition, the fluid in the external canal (normal participants) and the absence of the tympanic membrane and the ossicular chain (mastoidectomy patients) induced a conductive hearing loss (threshold elevation to air-conducted sounds coming from the bone vibrator), so that AC mechanisms were probably not involved in the thresholds to the fluid stimulation. In addition, as a result of the acoustic impedance mismatch between the fluid and skull bone, the audio-frequency vibrations induced in the fluid at threshold would probably not lead to vibrations of the bony wall of the meatus, so that hearing by osseous BC is not likely. Therefore, it seems that the thresholds to the fluid stimulation, in the absence of AC and of osseous BC, represent an example of STC, which is an additional mode of auditory stimulation in which the cochlea is activated by fluid pressures transmitted along a series of soft tissues, reaching and exciting the inner ear directly. STC can explain the mechanism of several auditory phenomena.
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Patel, Sunil, Vibhor Krishna, Joyce Nicholas, Charles M. Welzig, and Cristian Vera. "Preliminary observations on the vasomotor responses to electrical stimulation of the ventrolateral surface of the human medulla." Journal of Neurosurgery 117, no. 1 (July 2012): 150–55. http://dx.doi.org/10.3171/2012.3.jns11973.
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Object Pulsatile arterial compression (AC) of the ventrolateral medulla (VLM) is hypothesized to produce the hypertension in a subset of patients with essential hypertension. In animals, a network of subpial neuronal aggregates in the VLM has been shown to control cardiovascular functions. Although histochemically similar, neurons have been identified in the retro-olivary sulcus (ROS) of the human VLM, but their function is unclear. Methods The authors recorded cardiovascular responses to electrical stimulation at various locations along the VLM surface, including the ROS, in patients who were undergoing posterior fossa surgery for trigeminal neuralgia. This vasomotor mapping of the medullary surface was performed using a bipolar electrode, with stimulation parameters ranging from 5- to 30-second trains (20–100 Hz), constant current (1.5–5 mA), and 0.1-msec pulse durations. Heart rate (HR) and blood pressure (BP) were recorded continuously from baseline (10 seconds before the stimulus) up to 1 minute poststimulus. In 6 patients, 17 stimulation responses in BP and HR were recorded. Results The frequency threshold for any cardiovascular response was 20 Hz; the stimulation intensity threshold ranged from 1.5 to 3 mA. In the first patient, all stimulation responses were significantly different from sham recordings (which consisted of electrodes placed without stimulations). Repeated stimulations in the lower ROS produced similar responses in 3 other patients. Two additional patients had similar responses to single stimulations in the lower ROS. Olive stimulation produced no response (control). Hypotensive and/or bradycardic responses were consistently followed by a reflex hypertensive response. Slight right/left differences were noted. No patient suffered short- or long-term effects from this stimulation. Conclusions This stimulation technique for vasomotor mapping of the human VLM was safe and reproducible. Neuronal aggregates near the surface of the human ROS may be important in cardiovascular regulation. This method of vasomotor mapping with measures of responses in sympathetic tone (microneurography) should yield additional data for understanding the neuronal network that controls cardiovascular functions in the human VLM. Further studies in which a concentric bipolar electrode is used to generate this type of vasomotor map should also increase understanding of the pathophysiological mechanisms of neurogenically mediated hypertension, and assist in the design of studies to prove the hypothesis that it is caused by pulsatile AC of the VLM.
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Geibel, J., G. Giebisch, and W. F. Boron. "Effects of acetate on luminal acidification processes in the S3 segment of the rabbit proximal tubule." American Journal of Physiology-Renal Physiology 257, no. 4 (October 1, 1989): F586—F594. http://dx.doi.org/10.1152/ajprenal.1989.257.4.f586.
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We determined that, in the nominal absence of HCO-3, acetate (Ac-) doubles luminal acidification in the S3 segment of the rabbit proximal tubule. This stimulation had two components, one that was dependent on Na+ and luminal Ac- and a second that was independent of Na+ but dependent on basolateral Ac-. In the presence of 25 mM HCO-3, Ac- did not stimulate acid secretion (i.e., HCO-3 reabsorption), but actually inhibited it. The inhibition was 35% with bilateral Ac- and 15% with basolateral Ac-. The effects of Ac- were reversible both in the absence and presence of HCO-3, and are present at concentrations as low as 1 mM. We conclude that acetate (i.e., monocarboxylates) has a significant effect on luminal acidification processes both in the presence and absence of HCO-3.
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Ping, P., T. Anzai, M. Gao, and H. K. Hammond. "Adenylyl cyclase and G protein receptor kinase expression during development of heart failure." American Journal of Physiology-Heart and Circulatory Physiology 273, no. 2 (August 1, 1997): H707—H717. http://dx.doi.org/10.1152/ajpheart.1997.273.2.h707.
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We examined alterations in left ventricular (LV) G protein receptor kinase (GRK) and adenylyl cyclase (AC) isoform expression during the development of pacing-induced congestive heart failure (CHF). AC isoform and GRK expression were assessed 4 (mild CHF) and 28 (severe CHF) days after initiation of pacing. LV beta-adrenergic receptor (beta-AR) number and G protein content were unchanged by mild CHF. LV AC isoform mRNA content was unaltered by mild CHF, but there were increases in total GRK activity (P < 0.01), total GRK5 protein content (P < 0.04), and GRK5 mRNA (P = 0.003); total GRK2 protein content and GRK2 mRNA were unchanged. Mild CHF was associated with decreased beta-AR coupling (P < 0.01) and reduced beta-AR stimulation of AC (P < 0.05). Severe CHF was associated with LV beta-AR downregulation (P = 0.0001) and uncoupling (P < 0.001) and marked generalized reduction of AC activity (mean P = 0.01). LV ACVI isoform mRNA content was reduced (P = 0.002), but ACII and ACV isoform mRNA contents were unaffected. Persistent elevations in LV total GRK activity (P < 0.01), total GRK5 protein content (P < 0.001), and GRK5 mRNA (P = 0.01) were found; in contrast, total GRK2 protein content was unchanged and GRK2 mRNA was reduced (P = 0.02). These studies indicate that increased GRK activity is an early charge in heart failure that predates alterations in AC isoform expression. Impaired hormonal stimulation of AC, associated with beta-AR uncoupling, may result from increased GRK5 expression. AC downregulation is isoform specific and accompanies severe but not mild CHF.
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Ohbu, K., and R. A. Felder. "DA1 dopamine receptors in renal cortical collecting duct." American Journal of Physiology-Renal Physiology 261, no. 5 (November 1, 1991): F890—F895. http://dx.doi.org/10.1152/ajprenal.1991.261.5.f890.
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Renal dopamine DA1 receptors are linked to the regulation of sodium transport. We have previously reported the presence of DA1 receptors in the proximal convoluted tubule (PCT) but not in the distal convoluted tubule. However, the DA1 receptor in the collecting duct, the final determinant of electrolyte transport, has not been studied. DA1 receptors were studied in the microdissected cortical collecting duct (CCD) of rats by autoradiography with use of the selective DA1 radioligand 125I-Sch 23982 and by measurement of adenylate cyclase (AC) activity. Specific binding of 125I-Sch 23982 to CCD was saturable with radioligand concentration. The dissociation constant (Kd) was 0.46 +/- 0.08 nM (n = 5), and the maximum receptor density (Bmax) was 1.41 +/- 0.43 fmol/mg protein (n = 5). The DA1 antagonist Sch 23390 was more effective than the DA1 agonist fenoldopam in competing for specific 125I-Sch 23982 binding. Fenoldopam stimulated AC activity in CCD in a concentration-dependent (10(-9)-10(-6) M) manner. The ability of fenoldopam to stimulate AC activity was similar in CCD and PCT even though DA1 receptor density was 1,000 times greater in the CCD than in the PCT. In additional studies, fenoldopam stimulation of AC activity did not influence vasopressin-stimulated AC activity. We conclude that the DA1 receptor in rat CCD is tightly coupled to AC stimulation and that there is no interaction between DA1 agonist-stimulated and vasopressin-stimulated AC activity in the CCD.
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Schütte, Frank, Christof Burgdorf, Gert Richardt, and Thomas Kurz. "Adenosine A1 receptor-mediated inhibition of myocardial norepinephrine release involves neither phospholipase C nor protein kinase C but does involve adenylyl cyclase." Canadian Journal of Physiology and Pharmacology 84, no. 5 (May 2006): 573–77. http://dx.doi.org/10.1139/y06-007.
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Stimulation of adenosine A1 receptors in the heart exerts cardioprotective effects by inhibiting norepinephrine (NE) release from sympathetic nerve endings. The intraneuronal signal transduction triggered by presynaptic adenosine A1 receptors is still not completely understood. The objective of the present study was to determine whether phospholipase C (PLC), protein kinase C (PKC), and adenylyl cyclase (AC) are involved in the adenosine A1 receptor-mediated inhibition of endogenous (stimulation-induced) NE release in isolated Langendorff-perfused rat hearts as an approach to elucidate their role in the cardiovascular system. Activation of adenosine A1-receptors with 2-chloro-N6-cyclopentyladenosine (CCPA) decreased cardiac NE release by ~40%. Inhibition of PLC with 1-[6-[[(17b)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U 73122) as well as inhibition of PKC with 2-[1-(3-dimethylaminopropyl)indol-3-yl]-3-(indol-3-yl)maleimide (GF 109203X) slightly but significantly decreased NE release; however, the suppressive effect of CCPA on NE release was not modulated by U 73122 or GF 109203X. Blockade of AC with 9-(tetrahydro-2′-furyl)adenine (SQ 22536) reversed the inhibitory effect of CCPA on sympathetic neurotransmitter release irrespective of whether PKC was pharmacologically activated by phorbol 12-myristate 13-acetate or was not activated, indicating a PKC-independent but AC-dependent mechanism. Direct stimulation of AC with forskolin increased NE release by ∼20%; an effect that was antagonized by either CCPA or SQ 22536. These data suggest that the adenosine A1 receptor-mediated inhibition of NE release does not involve PLC or PKC but does involve AC.
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Adelman, Cahtia, Adi Cohen, Adi Regev-Cohen, Shai Chordekar, Rachel Fraenkel, and Haim Sohmer. "Air Conduction, Bone Conduction, and Soft Tissue Conduction Audiograms in Normal Hearing and Simulated Hearing Losses." Journal of the American Academy of Audiology 26, no. 01 (January 2015): 101–8. http://dx.doi.org/10.3766/jaaa.26.1.11.
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Background: In order to differentiate between a conductive hearing loss (CHL) and a sensorineural hearing loss (SNHL) in the hearing-impaired individual, we compared thresholds to air conduction (AC) and bone conduction (BC) auditory stimulation. The presence of a gap between these thresholds (an air-bone gap) is taken as a sign of a CHL, whereas similar threshold elevations reflect an SNHL. This is based on the assumption that BC stimulation directly excites the inner ear, bypassing the middle ear. However, several of the classic mechanisms of BC stimulation such as ossicular chain inertia and the occlusion effect involve middle ear structures. An additional mode of auditory stimulation, called soft tissue conduction (STC; also called nonosseous BC) has been demonstrated, in which the clinical bone vibrator elicits hearing when it is applied to soft tissue sites on the head, neck, and thorax. Purpose: The purpose of this study was to assess the relative contributions of threshold determinations to stimulation by STC, in addition to AC and osseous BC, to the differential diagnosis between a CHL and an SNHL. Research Design: Baseline auditory thresholds were determined in normal participants to AC (supra-aural earphones), BC (B71 bone vibrator at the mastoid, with 5 N application force), and STC (B71 bone vibrator) to the submental area and to the submandibular triangle with 5 N application force) stimulation in response to 0.5, 1.0, 2.0, and 4.0 kHz tones. A CHL was then simulated in the participants by means of an ear plug. Separately, an SNHL was simulated in these participants with 30 dB effective masking. Study sample: Study sample consisted of 10 normal-hearing participants (4 males; 6 females, aged 20–30 yr). Data Collection and Analysis: AC, BC, and STC thresholds were determined in the initial normal state and in the presence of each of the simulations. Results: The earplug-induced CHL simulation led to a mean AC threshold elevation of 21–37 dB (depending on frequency), but not of BC and STC thresholds. The masking-induced SNHL led to a mean elevation of AC, BC, and STC thresholds (23–36 dB, depending on frequency). In each type of simulation, the BC threshold shift was similar to that of the STC threshold shift. Conclusions: These results, which show a similar threshold shift for STC and for BC as a result of these simulations, together with additional clinical and laboratory findings, provide evidence that BC thresholds likely represent the threshold of the nonosseous BC (STC) component of multicomponent BC at the BC stimulation site, and thereby succeed in clinical practice to contribute to the differential diagnosis. This also provides evidence that STC (nonosseous BC) stimulation at low intensities probably does not involve components of the middle ear, represents true cochlear function, and therefore can also contribute to a differential diagnosis (e.g., in situations where the clinical bone vibrator cannot be applied to the mastoid or forehead with a 5 N force, such as in severe skull fracture).
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Torgan, C. E., and W. E. Kraus. "Regulation of type II adenylyl cyclase mRNA in rabbit skeletal muscle by chronic motor nerve pacing." American Journal of Physiology-Endocrinology and Metabolism 271, no. 2 (August 1, 1996): E253—E260. http://dx.doi.org/10.1152/ajpendo.1996.271.2.e253.
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Skeletal muscle exhibits a wide range in functional phenotype in response to changes in physiological demands. We have observed that, in response to changes in work patterns, alterations in gene expression of some proteins coincide with changes in adenylyl cyclase (AC) activity [Kraus, W.E., J.P. Longabaugh, and S. B. Liggett. Am. J. Physiol 263 (Endocrinol. Metab. 26): E266-E230, 1992]. We now examine AC isoform transcript prevalence in various rabbit skeletal muscles and in response to changing work demands. Using reverse transcriptase-polymerase chain reaction, we detected type II AC isoform transcripts in rabbit skeletal muscle. Ribonuclease protection analyses revealed that expression of the type II isoform significantly correlated with the percentage of fast-twitch type IIb/IId fibers (r2 = 0.765, P < 0.01). When a fast-twitch muscle was converted to a slow-twitch muscle via chronic electrical pacing, expression of type II AC mRNA significantly decreased. This response occurred 3 days after the onset of stimulation (78% decrease) and was still present after 21 days of stimulation (76% decrease). As type II AC is relatively insensitive to calcium regulation while sensitive to protein kinase C (PKC) signaling, these data provide further impetus for investigations of protein kinase A and PKC cross-talk signaling mechanisms in the regulation of gene expression.
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Gordeladze, J. O., I. Jynge, P. C. Borchgrevink та O. F. M. Sellevold. "Enhanced Responsiveness of the Myocardial β-Adrenoceptor-Adenylate Cyclase System in the Perfused Rat Heart (I)". Bioscience Reports 18, № 5 (1 жовтня 1998): 229–50. http://dx.doi.org/10.1023/a:1020156931565.
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Crude myocardial sarcolemmal membrane fractions were prepared from rat hearts subjected to total global ischemia with and without normoxic reperfusion, or global anoxic (N2) perfusion with and without normoxic reperfusion. The direct effects on β-adrenenoceptor number, G-protein levels and stimulation of the adenylate cyclase (AC) complex were assessed. In terms of AC activation, ischemia led to a marked increase (4-fold) in sensitivity to terbutaline (β2-agonist) and phorbol ester (tetradecanoyl phorbal acetate = TPA) stimulation, whereas the dobutamine (β1) responsiveness and Gpp(NH)p activation through GSα/Gi2α remained unaltered. However, forskolin-elicited holoenzyme activity fell markedly during normoxic reperfusion. Ischemia did not change the β1-adrenoceptor number, while β2-receptor population increased by approximately 45%. Western blots of myocardial GSA and Gi2α contents revealed that ischemia selectively diminished Gi2α levels only by some 50–70%. Contrastingly, anoxia selectively increased the AC sensitivity (2-fold) to β1-adrenergic stimulation. As subsequent to ischemia, anoxia also increased the sensitivy to TPA stimulation, however, only 2-fold. Gpp(NH)p activation was unchanged, while forskolin-enhanced activity gradually declined, also during ensuing normoxic reperfusion. Anoxia brought about a 75% enhancement in β1-receptor number, while β2-receptors remained unaffected. However, altered receptor number normalized on termination of normoxic reperfusion. Finally, anoxia led to a 50–60% decimation of myocardial Gi2α levels, while GSα was only marginally reduced. Despite the fact that the ischemia and anoxia effectuated a similar deterioration of physiological heart parameters, myocardial contents of energy rich phosphate moieties and loss of Gi2α, ischemia rendered the most profound increase in responsiveness of the sarcolemmal AC system.
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Yamazaki, Yoko, Masahiro Umino, Haruhisa Fukayama, and Masahiko Shimada. "The Effect of Alternating Current Iontophoresis on Rats with the Chronic Constriction Injury to the Infraorbital Nerve." International Journal of Dentistry 2012 (2012): 1–7. http://dx.doi.org/10.1155/2012/405292.
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This study aimed to examine the effect of AC iontophoresis on rats with the chronic constriction injury (CCI) to the infraorbital nerve by animal experiments. CCI model rats were divided into four groups, namely, rats that received general anesthesia for 60 min except AC IOP (CCI:n=5), AC IOP with 0.9% physiological saline for 60 min (CCI + saline AC IOP:n=5), AC IOP with 4% lidocaine hydrochloride for 60 min (CCI + lidocaine AC IOP:n=5), and attachment of two electrodes soaked with 4% lidocaine hydrochloride to the facial skin for 60 min (CCI + attach lidocaine:n=5). In the CCI + lidocaine AC IOP group, an elevated withdrawal threshold was observed after AC IOP, and the duration of efficacy was longer compared with that in the CCI + saline AC IOP and CCI + attached lidocaine groups. A significant decrease in the number of Fos-like immunoreactive (LI) cells was observed in the CCI + lidocaine AC IOP group compared with that in the CCI group. These findings suggest that the effect of CCI + lidocaine AC IOP group may be caused by active permeation of lidocaine into the facial skin and electrical stimulation of the trigeminal nucleus.
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Kurtz, A., J. Pfeilschifter, C. D. Brown, and C. Bauer. "NaCl transport stimulates prostaglandin release in cultured renal epithelial (MDCK) cells." American Journal of Physiology-Cell Physiology 250, no. 5 (May 1, 1986): C676—C681. http://dx.doi.org/10.1152/ajpcell.1986.250.5.c676.
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Prostaglandins (PGs) can modulate a variety of renal functions, including Na+ and Cl- reabsorption. However, it is not known if a direct interdependence exists between PG synthesis and transport activity. The present study was done to find out whether or not the rate of NaCl transport has an influence on PG synthesis in renal tubular cells. For our studies we used cultures of so-called high-resistance MDCK cells, which were originally derived from canine kidney. This cell type has a loop diuretic- and ouabain-sensitive NaCl transport that can be enhanced by activation of the adenylate cyclase (AC). In MDCK cell cultures we found that each state of increased NaCl transport during stimulation of AC by either epinephrine (10(-6) M), isoprenaline (10(-5) M), or forskolin (10(-5) M) was accompanied by a twofold increase in PG release. During inhibition of NaCl transport by furosemide (10(-4) M) or ouabain (2 X 10(-4) M), stimulation of AC failed to increase PGE2 release, whereas basal PG production was not inhibited by either furosemide or ouabain. Furthermore, PG formation during activation of AC was dependent on the concentration of extracellular Na+, whereas PG formation in the absence of activators of AC was independent of extracellular Na+. These results suggest that increased NaCl transport stimulates PG formation in cultures of high-resistance MDCK cells.
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JUšKA, Alfonsas, and Richard W. FARNDALE. "Inhibition of human platelet adenylate cyclase activity by adrenaline, thrombin and collagen: analysis and reinterpretation of experimental data." Biochemical Journal 340, no. 1 (May 10, 1999): 245–53. http://dx.doi.org/10.1042/bj3400245.
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Mathematical models based on the current understanding of stimulation and inhibition of adenylate cyclase (AC) activity have been developed and used to analyse experimental data [Farndale, Winkler, Martin and Barnes (1992) Biochem. J. 282, 25-32] describing the inhibition of human platelet AC by collagen, thrombin and adrenaline. Here it has been demonstrated that neither affinities of receptors specific for adrenaline or thrombin nor the activity of cAMP phosphodiesterase are affected by collagen. Both collagen and thrombin at high doses act as effective inhibitors of AC activity. Inhibition of AC activity by collagen proceeds via two parallel pathways; the same is true for thrombin at moderate concentrations, and the two ligands act independently. The G-protein-dependence of these pathways is distinct from that mediating inhibition of AC activity by adrenaline, i.e. Gi2. Convergence of the inhibitory pathways takes place at the catalytic subunit of AC.
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Trimble, R. M., and Ashraf M. El-Sayed. "Effect of certain monounsaturated dodecene and tetradecene acetates and alcohols on electroantennogram response and pheromone-mediated trap catch of the obliquebanded leafroller." Canadian Entomologist 138, no. 2 (April 2006): 218–27. http://dx.doi.org/10.4039/n05-067.
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AbstractThe effect of certain monounsaturated dodecene and tetradecene acetates and alcohols on electroantennogram (EAG) response and pheromone-mediated trap catch was examined in male obliquebanded leafroller moths, Choristoneura rosaceana (Harris) (Lepidoptera: Tortricidae). The stimulation of antennae with 0.1 ng of (Z)-11-tetradecenyl acetate (Z11-14:Ac), the major pheromone compound of this species, elicited an EAG response. The use of 1 ng of (Z)-9-tetradecenyl acetate (Z9-14:Ac) or (E)-9-tetradecenyl acetate (E9-14:Ac) or 10 ng of (Z)-9-dodecenyl acetate (Z9-12:Ac) or (E)-9-dodecenyl acetate (E9-12:Ac) was required to elicit a response. One hundred nanograms of (E)-9-tetradecenol (E9-14:OH) were required to elicit a response from antennae. The stimulation of antennae with up to 100 ng of (Z)-9-tetradecenol (Z9-14:OH) did not elicit a response. The addition of 0.1 mg of Z9-12:Ac to 1 mg of synthetic C. rosaceana pheromone consisting of a 100:2:1.5:1 blend of Z11-14:Ac, (E)-11-tetradecenyl acetate, (Z)-11-tetradecenol, and (Z)-11-tetradecenal reduced the capture of moths in pheromone-baited traps by more than 72%. Trap catch was reduced by more than 90% by the addition of 0.01 mg of Z9-14:Ac or E9-14:Ac to 1 mg of C. rosaceana pheromone. There was no detectable reduction in trap catch when 1 mg of E9-12:Ac, Z9-14:OH, or E9-14:OH was added to 1 mg of C. rosaceana pheromone. There was a greater than 95% reduction in trap catch when sources of Z9- or E9-12:Ac were mounted at the entrances to traps, 10 cm from the pheromone source. Trap catch was not affected by placing sources of Z9- or E9-14:Ac at trap entrances. Four 1 or 10 mg sources of E9-14:Ac placed 1 m from a trap did not affect the number of male C. rosaceana captured. The study demonstrates that although a compound may have profound attraction inhibiting activity when mixed directly with C. rosaceana pheromone, this activity may be lost if the inhibitor is emitted a short distance from the pheromone. The study also demonstrates that a potent attraction inhibitor such as E9-14:Ac does not repel C. rosaceana males and must be present along with pheromone to affect the behavior of this species.
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Geal-Dor, Miriam, Shai Chordekar, Cahtia Adelman, Michal Kaufmann-Yehezkely, and Haim Sohmer. "Audiogram in Response to Stimulation Delivered to Fluid Applied to the External Meatus." Journal of Audiology and Otology 24, no. 2 (April 10, 2020): 79–84. http://dx.doi.org/10.7874/jao.2019.00388.
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Background and Objectives: Hearing can be elicited in response to vibratory stimuli delivered to fluid in the external auditory meatus. To obtain a complete audiogram in subjects with normal hearing in response to pure tone vibratory stimuli delivered to fluid applied to the external meatus.Subjects and Methods: Pure tone vibratory stimuli in the audiometric range from 0.25 to 6.0 kHz were delivered to fluid applied to the external meatus of eight participants with normal hearing (15 dB or better) using a rod attached to a standard clinical bone vibrator. The fluid thresholds obtained were compared to the air conduction (AC), bone conduction (BC; mastoid), and soft tissue conduction (STC; neck) thresholds in the same subjects.Results: Fluid stimulation thresholds were obtained at every frequency in each subject. The fluid and STC (neck) audiograms sloped down at higher frequencies, while the AC and BC audiograms were flat. It is likely that the fluid stimulation audiograms did not involve AC mechanisms or even, possibly, osseous BC mechanisms.Conclusions: The thresholds elicited in response to the fluid in the meatus likely reflect a form of STC and may result from excitation of the inner ear by the vibrations induced in the fluid. The sloping fluid audiograms may reflect transmission pathways that are less effective at higher frequencies.
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Izawa, T., T. Komabayashi, T. Mochizuki, K. Suda, and M. Tsuboi. "Enhanced coupling of adenylate cyclase to lipolysis in permeabilized adipocytes from trained rats." Journal of Applied Physiology 71, no. 1 (July 1, 1991): 23–29. http://dx.doi.org/10.1152/jappl.1991.71.1.23.
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Digitonin-permeabilized adipocytes were used to study the coupling of adenylate cyclase (AC) to lipolysis in exercise-trained rats. Isoproterenol-(IPR) stimulated lipolysis in permeabilized cells was significantly greater in trained than in control rats. Under essentially identical conditions, the dose-response curve for IPR stimulation of AC activity in the absence of 3-isobutyl-1-methylxanthine was similar in trained and control rats. However, the potency of stimulation by IPR as a percentage of the basal level was greater in trained rats. AC activity and lipolysis in the presence of 3-isobutyl-1-methylxanthine were also significantly greater in trained than in control rats. Least-squares analysis by plotting the log AC vs. lipolysis values showed that the regression coefficient was about three-fold greater in trained than in control rats. The concentration of endogenous adenosine 3′,5′-cyclic monophosphate (cAMP) needed to produce a half-maximal lipolytic response was 18.58 and 10.81 pmol.min-1.10(6) cells-1 in control and trained rats, respectively. Thus a positive relationship existed between lipolysis and AC activity, with a tighter coupling in trained rats. Lipolysis in response to exogenous cAMP tended to be greater in trained than in control rats, and the difference was statistically significant for 50 microM and 10 mM cAMP. Our finding support the concept that the major mechanism of enhanced lipolysis in trained rats was an increase in the activity of enzymatic step(s) distal to cAMP.
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Zhang, Zhuo, Chun-Hua Liu, Yan-Qin Yu, Kenji Fujimoto, Ying-Shing Chan, and Jufang He. "Corticofugal Projection Inhibits the Auditory Thalamus Through the Thalamic Reticular Nucleus." Journal of Neurophysiology 99, no. 6 (June 2008): 2938–45. http://dx.doi.org/10.1152/jn.00002.2008.
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Electrical stimulation of the auditory cortex (AC) causes both facilitatory and inhibitory effects on the medial geniculate body (MGB). The purpose of this study was to identify the corticofugal inhibitory pathway to the MGB. We assessed two potential circuits: 1) the cortico-colliculo-thalamic circuit and 2) cortico-reticulo-thalamic one. We compared intracellular responses of MGB neurons to electrical stimulation of the AC following bilateral ablation of the inferior colliculi (IC) or thalamic reticular nucleus (TRN) in anesthetized guinea pigs. Cortical stimulation with intact TRN could cause strong inhibitory effects on the MGB neurons. The corticofugal inhibition remained effective after bilateral IC ablation, but it was minimized after the TRN was lesioned with kainic acid. Synchronized TRN neuronal activity and MGB inhibitory postsynaptic potentials (IPSPs) were observed with multiple recordings. The results suggest that corticofugal inhibition traverses the corticoreticulothalamic pathway, indicating that the colliculi-geniculate inhibitory pathway is probably only for feedforward inhibition.
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Zou, H., R. R. A. Syms, S. Mellon, and K. E. Tanner. "MEMS Dielectrophoresis Device for Osteoblast Cell Stimulation." Advanced Materials Research 60-61 (January 2009): 63–67. http://dx.doi.org/10.4028/www.scientific.net/amr.60-61.63.
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A fixed microelectrode device for cell stimulation has been designed and fabricated using micro-electromechanical systems (MEMS) technology. Dielectrophoretic forces obtained from non-uniform electric fields were used for manipulating and positioning osteoblasts. The experiments show that the osteoblasts experience positive dielectrophoresis (p-DEP) when suspended in iso-osmotic culture medium and exposed to AC fields at 5 MHz frequency. This work will help to investigate the mechanisms underlying Wolff’s law of bone growth dynamics at the cellular level. The methods used can also be developed to control osteoblast metabolism and ultimately enhance bone repair processes.
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Doucet, A., C. Barlet-Bas, S. Siaume-Perez, C. Khadouri, and S. Marsy. "Gluco- and mineralocorticoids control adenylate cyclase in specific nephron segments." American Journal of Physiology-Renal Physiology 258, no. 4 (April 1, 1990): F812—F820. http://dx.doi.org/10.1152/ajprenal.1990.258.4.f812.
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Adrenal insufficiency is associated with an impairment of kidney diluting and concentrating ability, defects that may result from alterations of vasopressin-induced adenosine 3',5'-cyclic monophosphate (cAMP) production. The purpose of this study were 1) to localize the sites of decreased vasopressin-stimulated adenylate cyclase (AC) activity along the nephron of adrenalectomized rats; 2) to determine whether the response of AC to other hormones is altered by adrenalectomy; 3) to evaluate whether changes in AC are due to the deficiency in mineralocorticoids and/or glucocorticoids; and 4) to characterize the mechanism of action of corticosteroids on the AC system. Results indicate that adrenalectomy reduced AC stimulation by vasopressin, glucagon, and calcitonin in the thick ascending limb, whereas only the response to vasopressin decreased in the collecting tubule. Glucocorticoid administration curtailed adrenalectomy-induced alterations of AC in the thick ascending limb, whereas that in the collecting tubule was prevented by mineralocorticoids. Adrenalectomy did not alter forskolin-stimulated AC, whereas it decreased responses to aluminum fluoride and cholera toxin. Finally, alterations of fluoride- and cholera toxin-stimulated AC were prevented by glucocorticoid and mineralocorticoid repletion in the thick ascending limb and collecting tubule, respectively.
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Zhu, Zhi-ru, Fenglian Xu, Wei-gang Ji, Shuan-cheng Ren, Fang Chen, Peng-zhi Chen, Hui-hui Jiang, et al. "Synaptic mechanisms underlying thalamic activation-induced plasticity in the rat auditory cortex." Journal of Neurophysiology 111, no. 9 (May 1, 2014): 1746–58. http://dx.doi.org/10.1152/jn.00180.2013.
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Electrical stimulation of ventral division of medial geniculate body (MGBv) neurons evokes a shift of the frequency-tuning curves of auditory cortical (AC) neurons toward the best frequency (BF) of the stimulated MGBv neurons (frequency-specific plasticity). The shift of BF is induced by inhibition of responses at the BF of the recorded AC neuron, with coincident facilitation of responses at the BF of the stimulated MGBv neuron. However, the synaptic mechanisms are not yet understood. We hypothesize that activation of thalamocortical synaptic transmission and receptor function may contribute to MGBv stimulation-induced frequency-specific auditory plasticity and the shift of BF. To test this hypothesis, we measured changes in the excitatory postsynaptic currents in pyramidal neurons of layer III/IV in the auditory cortex following high-frequency stimulation (HFS) of the MGBv, using whole cell recordings in an auditory thalamocortical slice. Our data showed that in response to the HFS of the MGBv the excitatory postsynaptic currents of AC neurons showed long-term bidirectional synaptic plasticity and long-term potentiation and depression. Pharmacological studies indicated that the long-term synaptic plasticity was induced through the activation of different sets of N-methyl-d-aspartate-type glutamatergic receptors, γ-aminobutyric acid-type receptors, and type 5 metabotropic glutamate receptors. Our data further demonstrated that blocking of different receptors with specific antagonists significantly inhibited MGBv stimulation-induced long-term plasticity as well as the shift of BF. These data indicate that these receptors have an important role in mediating frequency-specific auditory cortical plasticity.
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Richardson, Mark. "Deep Brain Stimulation for Locomotor Recovery Following Spinal Cord Injury." Neurosurgery 74, no. 2 (February 2014): N18—N19. http://dx.doi.org/10.1227/01.neu.0000442979.07078.ac.
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Goddard, Ayana A., Carolyn S. Pierce, and Kenneth J. McLeod. "Reversal of Lower Limb Edema by Calf Muscle Pump Stimulation." Journal of Cardiopulmonary Rehabilitation and Prevention 28, no. 3 (May 2008): 174–79. http://dx.doi.org/10.1097/01.hcr.0000320067.58599.ac.
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Martínez, C., J. Modolell, and J. Garrell. "Regulation of the proneural gene achaete by helix-loop-helix proteins." Molecular and Cellular Biology 13, no. 6 (June 1993): 3514–21. http://dx.doi.org/10.1128/mcb.13.6.3514.
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The Achaete (Ac) protein, a transcriptional regulator of the basic-helix-loop-helix (bHLH) type, confers upon ectodermal cells the ability to become neural precursors. Its temporally and spatially regulated expression, together with that of the related Scute (Sc) protein, helps define the pattern of Drosophila melanogaster sensory organs. We have examined the transcriptional control of the ac gene and shown, using in vivo assays, that several E-boxes, putative interacting sites for bHLH proteins, present in the ac promoter are most important for ac regulation. They most likely mediate ac self-stimulation and sc trans-activation. We also demonstrate that ac transcription is negatively regulated in vivo by the gene extramacrochaetae (emc) in a manner dependent on Ac and Sc products. emc encodes an HLH protein that lacks the basic region and presumably antagonizes Ac and Sc function by sequestering these proteins in complexes unable to interact with DNA. Our results strongly support the model of negative regulation of emc on ac and sc transcription through titration of their products. As currently thought, this seems accomplished by heterodimerization via the HLH domain, because an amino acid substitution in this region abolishes the emc antagonistic effect both in vitro and in vivo.
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Martínez, C., J. Modolell, and J. Garrell. "Regulation of the proneural gene achaete by helix-loop-helix proteins." Molecular and Cellular Biology 13, no. 6 (June 1993): 3514–21. http://dx.doi.org/10.1128/mcb.13.6.3514-3521.1993.
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The Achaete (Ac) protein, a transcriptional regulator of the basic-helix-loop-helix (bHLH) type, confers upon ectodermal cells the ability to become neural precursors. Its temporally and spatially regulated expression, together with that of the related Scute (Sc) protein, helps define the pattern of Drosophila melanogaster sensory organs. We have examined the transcriptional control of the ac gene and shown, using in vivo assays, that several E-boxes, putative interacting sites for bHLH proteins, present in the ac promoter are most important for ac regulation. They most likely mediate ac self-stimulation and sc trans-activation. We also demonstrate that ac transcription is negatively regulated in vivo by the gene extramacrochaetae (emc) in a manner dependent on Ac and Sc products. emc encodes an HLH protein that lacks the basic region and presumably antagonizes Ac and Sc function by sequestering these proteins in complexes unable to interact with DNA. Our results strongly support the model of negative regulation of emc on ac and sc transcription through titration of their products. As currently thought, this seems accomplished by heterodimerization via the HLH domain, because an amino acid substitution in this region abolishes the emc antagonistic effect both in vitro and in vivo.
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Farrell, Diane M., Chih-Chang Wei, José Tallaj, Jeffrey L. Ardell, J. Andrew Armour, Gilbert R. Hageman, Wayne E. Bradley, and Louis J. Dell'Italia. "Angiotensin II modulates catecholamine release into interstitial fluid of canine myocardium in vivo." American Journal of Physiology-Heart and Circulatory Physiology 281, no. 2 (August 1, 2001): H813—H822. http://dx.doi.org/10.1152/ajpheart.2001.281.2.h813.
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This study tested the hypothesis that exogenous infusion of angiotensin II (ANG II) leads to the release of catecholamines [norepinephrine (NE) and epinephrine (EPI)] into the cardiac interstitial fluid (ISF) space of dogs with adrenals intact (AI) ( n = 7) and with adrenals clamped (AC) ( n = 5). LV ISF samples were collected at 3-min intervals during administration of ANG II (100 μM ANG II at 1 ml/min for 10 min) to right atrial neurons via their local arterial blood supply and during electrical stimulation of the stellate ganglia of open-chest anesthetized dogs. In AI dogs, ANG II caused ISF NE to increase fivefold ( P < 0.05) without a significant increase in coronary sinus (CS) NE. Electrical stimulation (5 ms, 4 Hz, 8–14 V, and 10 min) of the stellate ganglia caused a similar increase in ISF NE ( P < 0.05), accompanied by a sevenfold increase in CS NE ( P < 0.05). ISF EPI increased greater than sixfold during ANG II infusion ( P < 0.05) and during stellate stimulation. However, during ANG II infusions, aorta plasma EPI levels increased fourfold in AI dogs, whereas in AC dogs, CS NE and EPI levels were unaffected during ANG II infusions. Nevertheless, baseline ISF NE and EPI did not differ and increased to a similar extent during ANG II infusions in AI versus AC dogs. Thus exogenously administered ANG II increases the amount of NE liberated into the ISF independent of the adrenal contribution, the amount matching that induced by electrical stimulation of all cardiac sympathetic efferent neurons. In contrast, NE spillover into the CS occurred only during electrical stimulation of stellate ganglia. NE release and uptake mechanisms within the myocardium are differently affected, depending on how the final common pathway of the sympathetic efferent nervous system is modified.
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Sun, Wei, Dalian Ding, Sam Reyes, and Richard J. Salvi. "Effects of AC and DC stimulation on chinchilla SOAE amplitude and frequency." Hearing Research 150, no. 1-2 (December 2000): 137–48. http://dx.doi.org/10.1016/s0378-5955(00)00195-7.
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Debleds, S., J. P. Rebrasse, L. Dantas de Morais, I. Frapreau, R. Perdreau, and B. Morillon. "Localization of sensitive areas of power AC switch under thermal laser stimulation." Microelectronics Reliability 47, no. 9-11 (September 2007): 1569–73. http://dx.doi.org/10.1016/j.microrel.2007.07.018.
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BOND, W., and PHILIPPA J. BURCH. "Stimulation of weed seed germination by 1–(3-chlorophthalirnido) cyclohexanecarboxamide (AC 94377)." Annals of Applied Biology 116, no. 1 (February 1990): 119–30. http://dx.doi.org/10.1111/j.1744-7348.1990.tb06591.x.
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Miyagi, Yasushi, Fumio Shima, and Tomio Sasaki. "Brain shift: an error factor during implantation of deep brain stimulation electrodes." Journal of Neurosurgery 107, no. 5 (November 2007): 989–97. http://dx.doi.org/10.3171/jns-07/11/0989.
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Object The goal of this study was to focus on the tendency of brain shift during stereotactic neurosurgery and the shift's impact on the unilateral and bilateral implantation of electrodes for deep brain stimulation (DBS). Methods Eight unilateral and 10 bilateral DBS electrodes at 10 nuclei ventrales intermedii and 18 subthalamic nuclei were implanted in patients at Kaizuka Hospital with the aid of magnetic resonance (MR) imaging–guided and microelectrode-guided methods. Brain shift was assessed as changes in the 3D coordinates of the anterior and posterior commissures (AC and PC) with MR images before and immediately after the implantation surgery. The positions of the implanted electrodes, based on the midcommissural point and AC–PC line, were measured both on x-ray films (virtual position) during surgery and the postoperative MR images (actual position) obtained on the 7th day postoperatively. Results Contralateral and posterior shift of the AC and PC were the characteristics of unilateral and bilateral procedures, respectively. The authors suggest the following. 1) The first unilateral procedure elicits a unilateral air invasion, resulting in a contralateral brain shift. 2) During the second procedure in the bilateral surgery, the contralateral shift is reset to the midline and, at the same time, the anteroposterior support by the contralateral hemisphere against gravity is lost due to a bilateral air invasion, resulting in a significant posterior (caudal) shift. Conclusions To note the tendency of the brain to shift is very important for accurate implantation of a DBS electrode or high frequency thermocoagulation, as well as for the prediction of therapeutic and adverse effects of stereotactic surgery.
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Teitelbaum, I., and T. Berl. "Increased cytosolic Ca2+ inhibits AVP-stimulated adenylyl cyclase activity in rat IMCT cells by activation of PKC." American Journal of Physiology-Renal Physiology 266, no. 3 (March 1, 1994): F486—F490. http://dx.doi.org/10.1152/ajprenal.1994.266.3.f486.
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In rat inner medullary collecting tubule (RIMCT) cells increasing cytosolic Ca2+ with a calcium ionophore inhibits arginine vasopressin (AVP)-stimulated adenylyl cyclase (AC). Inhibition by Ca2+ is not observed in pertussis toxin (PT)-treated cells, indicating a role for the inhibitory G protein, Gi. The mechanism of activation of Gi remains to be determined. We examined the hypothesis that inhibition of AVP-stimulated AC by increased cytosolic Ca2+ is due to activation of protein kinase C (PKC). Preincubation of RIMCT cells with ionophore results in inhibition of AVP-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) formation. To assess whether stimulation of phospholipase C (PLC) and therefore activation of PKC occurs with ionophore and AVP, inositol trisphosphate (IP3) production was measured. Incubation of RIMCT cells with either 10(-7) M AVP or ionophore results in IP3 production that is no different from basal. However, simultaneous exposure to 100 nM AVP with ionophore results in marked enhancement of IP3 production clearly reflecting stimulation of PLC in this setting. Stimulation of PLC is not observed in PT-treated cells. Likewise, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), an inhibitor of PKC, mimics the effect of PT to prevent inhibition of AVP-stimulated AC by ionophore, but N-(2-[methylamino]ethyl)-5-isoquinolinesulfonamide (H-8), an inhibitor of protein kinase A (PKA), does not. As is the case when PKC is stimulated directly with a phorbol ester, exposure to ionomycin inhibits the response to AVP but does not alter the response to isoproterenol. These studies demonstrate that increased cytosolic Ca2+ does not, as previously postulated, inhibit AC by a direct effect on Gi. Rather, when cytosolic Ca2+ is increased, AVP stimulates PLC; the ensuring activation of PKC inhibits cAMP formation.