Academic literature on the topic 'KB-R7943'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Contents
Consult the lists of relevant articles, books, theses, conference reports, and other scholarly sources on the topic 'KB-R7943.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Journal articles on the topic "KB-R7943"
1
Magee, William P., Gayatri Deshmukh, Michael P. Deninno, Jill C. Sutt, Justin G. Chapman, and W. Ross Tracey. "Differing cardioprotective efficacy of the Na+/Ca2+ exchanger inhibitors SEA0400 and KB-R7943." American Journal of Physiology-Heart and Circulatory Physiology 284, no. 3 (March 1, 2003): H903—H910. http://dx.doi.org/10.1152/ajpheart.00784.2002.
Full textAbstract:
KB-R7943 and SEA0400 are Na+/Ca2+ exchanger (NCX) inhibitors with differing potency and selectivity. The cardioprotective efficacy of these NCX inhibitors was examined in isolated rabbit hearts (Langendorff perfused) subjected to regional ischemia (coronary artery ligation) and reperfusion. KB-R7943 and SEA0400 elicited concentration-dependent reductions in infarct size (SEA0400 EC50: 5.7 nM). SEA0400 was more efficacious than KB-R7943 (reduction in infarct size at 1 μM: SEA0400, 75%; KB-R7943, 40%). Treatment with either inhibitor yielded similar reductions in infarct size whether administered before or after regional ischemia. SEA0400 (1 μM) improved postischemic recovery of function (±dP/d t), whereas KB-R7943 impaired cardiac function at ≥1 μM. At 5–20 μM, KBR-7943 elicited rapid and profound depressions of heart rate, left ventricular developed pressure, and ±dP/d t. Thus the ability of KB-R7943 to provide cardioprotection is modest and limited by negative effects on cardiac function, whereas the more selective NCX inhibitor SEA0400 elicits marked reductions in myocardial ischemic injury and improved ±dP/d t. NCX inhibition represents an attractive approach for achieving clinical cardioprotection.
2
Elias, Chadwick L., Anton Lukas, Sabin Shurraw, Jason Scott, Alexander Omelchenko, Gil J. Gross, Mark Hnatowich, and Larry V. Hryshko. "Inhibition of Na+/Ca2+ exchange by KB-R7943: transport mode selectivity and antiarrhythmic consequences." American Journal of Physiology-Heart and Circulatory Physiology 281, no. 3 (September 1, 2001): H1334—H1345. http://dx.doi.org/10.1152/ajpheart.2001.281.3.h1334.
Full textAbstract:
The Na+/Ca2+ exchanger plays a prominent role in regulating intracellular Ca2+ levels in cardiac myocytes and can serve as both a Ca2+ influx and efflux pathway. A novel inhibitor, KB-R7943, has been reported to selectively inhibit the reverse mode (i.e. , Ca2+ entry) of Na+/Ca2+ exchange transport, although many aspects of its inhibitory properties remain controversial. We evaluated the inhibitory effects of KB-R7943 on Na+/Ca2+exchange currents using the giant excised patch-clamp technique. Membrane patches were obtained from Xenopus laevis oocytes expressing the cloned cardiac Na+/Ca2+exchanger NCX1.1, and outward, inward, and combined inward-outward currents were studied. KB-R7943 preferentially inhibited outward (i.e., reverse) Na+/Ca2+ exchange currents. The inhibitory mechanism consists of direct effects on the transport machinery of the exchanger, with additional influences on ionic regulatory properties. Competitive interactions between KB-R7943 and the transported ions were not observed. The antiarrhythmic effects of KB-R7943 were then evaluated in an ischemia-reperfusion model of cardiac injury in Langendorff-perfused whole rabbit hearts using electrocardiography and measurements of left ventricular pressure. When 3 μM KB-R7943 was applied for 10 min before a 30-min global ischemic period, ventricular arrhythmias (tachycardia and fibrillation) associated with both ischemia and reperfusion were almost completely suppressed. The observed electrophysiological profile of KB-R7943 and its protective effects on ischemia-reperfusion-induced ventricular arrhythmias support the notion of a prominent role of Ca2+ entry via reverse Na+/Ca2+ exchange in this process.
3
Chorro, Francisco J., Isabel Trapero, Luis Such-Miquel, Francisca Pelechano, Luis Mainar, Joaquín Cánoves, Álvaro Tormos, et al. "Pharmacological modifications of the stretch-induced effects on ventricular fibrillation in perfused rabbit hearts." American Journal of Physiology-Heart and Circulatory Physiology 297, no. 5 (November 2009): H1860—H1869. http://dx.doi.org/10.1152/ajpheart.00144.2009.
Full textAbstract:
Stretch induces modifications in myocardial electrical and mechanical activity. Besides the effects of substances that block the stretch-activated channels, other substances could modulate the effects of stretch through different mechanisms that affect Ca2+ handling by myocytes. Thirty-six Langendorff-perfused rabbit hearts were used to analyze the effects of the Na+/Ca2+ exchanger blocker KB-R7943, propranolol, and the adenosine A2 receptor antagonist SCH-58261 on the acceleration of ventricular fibrillation (VF) produced by acute myocardial stretching. VF recordings were obtained with two epicardial multiple electrodes before, during, and after local stretching in four experimental series: control ( n = 9), KB-R7943 (1 μM, n = 9), propranolol (1 μM, n = 9), and SCH-58261 (1 μM, n = 9). Both the Na+/Ca2+ exchanger blocker KB-R7943 and propranolol induced a significant reduction ( P < 0.001 and P < 0.05, respectively) in the dominant frequency increments produced by stretching with respect to the control and SCH-58261 series (control = 49.9%, SCH-58261 = 52.1%, KB-R7943 = 9.5%, and propranolol = 12.5%). The median of the activation intervals, the functional refractory period, and the wavelength of the activation process during VF decreased significantly under stretch in the control and SCH-58261 series, whereas no significant variations were observed in the propranolol and KB-R7943 series, with the exception of a slight but significant decrease in the median of the fibrillation intervals in the KB-R7943 series. KB-R7943 and propranolol induced a significant reduction in the activation maps complexity increment produced by stretch with respect to the control and SCH-58261 series. In conclusion, the electrophysiological effects responsible for stretch-induced VF acceleration in the rabbit heart are reduced by the Na+/Ca2+ exchanger blocker KB-R7943 and by propranolol but not by the adenosine A2 receptor antagonist SCH-58261.
4
Pezier, A., Y. V. Bobkov, and B. W. Ache. "The Na+/Ca2+ Exchanger Inhibitor, KB-R7943, Blocks a Nonselective Cation Channel Implicated in Chemosensory Transduction." Journal of Neurophysiology 101, no. 3 (March 2009): 1151–59. http://dx.doi.org/10.1152/jn.90903.2008.
Full textAbstract:
The mechanism(s) of olfactory transduction in invertebrates remains to be fully understood. In lobster olfactory receptor neurons (ORNs), a nonselective sodium-gated cation (SGC) channel, a presumptive transient receptor potential (TRP)C channel homolog, plays a crucial role in olfactory transduction, at least in part by amplifying the primary transduction current. To better determine the functional role of the channel, it is important to selectively block the channel independently of other elements of the transduction cascade, causing us to search for specific pharmacological blockers of the SGC channel. Given evidence that the Na+/Ca2+ exchange inhibitor, KB-R7943, blocks mammalian TRPC channels, we studied this probe as a potential blocker of the lobster SGC channel. KB-R7943 reversibly blocked the SGC current in both inside- and outside-out patch recordings in a dose- and voltage-dependent manner. KB-R7943 decreased the channel open probability without changing single channel amplitude. KB-R7943 also reversibly and in a dose-dependent manner inhibited both the odorant-evoked discharge of lobster ORNs and the odorant-evoked whole cell current. Our findings strongly imply that KB-R7943 potently blocks the lobster SGC channel and likely does so directly and not through its ability to block the Na+/Ca2+ exchanger.
5
Yamamura, Hisao, William C. Cole, Satomi Kita, Shingo Hotta, Hidemichi Murata, Yoshiaki Suzuki, Susumu Ohya, Takahiro Iwamoto, and Yuji Imaizumi. "Overactive bladder mediated by accelerated Ca2+influx mode of Na+/Ca2+exchanger in smooth muscle." American Journal of Physiology-Cell Physiology 305, no. 3 (August 1, 2013): C299—C308. http://dx.doi.org/10.1152/ajpcell.00065.2013.
Full textAbstract:
The Na+/Ca2+exchanger (NCX) is thought to be a key molecule in the regulation of cytosolic Ca2+dynamics. The relative importance of the two Ca2+transport modes of NCX activity leading to Ca2+efflux (forward) and influx (reverse) in smooth muscle, however, remains unclear. Unexpectedly, spontaneous contractions of urinary bladder smooth muscle (UBSM) were enhanced in transgenic mice overexpressing NCX1.3 (NCX1.3tg/tg). The enhanced activity was attenuated by KB-R7943 or SN-6. Whole cell outward NCX current sensitive to KB-R7943 or Ni2+was readily detected in UBSM cells from NCX1.3tg/tgbut not wild-type mice. Spontaneous Ca2+transients in myocytes of NCX1.3tg/tgwere larger and frequently resulted in propagating events and global elevations in cytosolic Ca2+concentration. Significantly, NCX1.3tg/tgmice exhibited a pattern of more frequent urination of smaller volumes and this phenotype was reversed by oral administration of KB-R7943. On the other hand, KB-R7943 did not improve it in KB-R7943-insensitive (G833C-)NCX1.3tg/tgmice. We conclude that NCX1.3 overexpression is associated with abnormal urination owing to enhanced Ca2+influx via reverse mode NCX leading to prolonged, propagating spontaneous Ca2+release events and a potentiation of spontaneous UBSM contraction. These findings suggest the possibility that NCX is a candidate molecular target for overactive bladder therapy.
6
Kim, Moon Young, Geun Hee Seol, Guo Hua Liang, Ji Aee Kim, and Suk Hyo Suh. "Na+-K+ pump activation inhibits endothelium-dependent relaxation by activating the forward mode of Na+/Ca2+ exchanger in mouse aorta." American Journal of Physiology-Heart and Circulatory Physiology 289, no. 5 (November 2005): H2020—H2029. http://dx.doi.org/10.1152/ajpheart.00908.2004.
Full textAbstract:
The effect of Na+-K+ pump activation on endothelium-dependent relaxation (EDR) and on intracellular Ca2+ concentration ([Ca2+]i) was examined in mouse aorta and mouse aortic endothelial cells (MAECs). The Na+-K+ pump was activated by increasing extracellular K+ concentration ([K+]o) from 6 to 12 mM. In aortic rings, the Na+ ionophore monensin evoked EDR, and this EDR was inhibited by the Na+/Ca2+ exchanger (NCX; reverse mode) inhibitor KB-R7943. Monensin-induced Na+ loading or extracellular Na+ depletion (Na+ replaced by Li+) increased [Ca2+]i in MAECs, and this increase was inhibited by KB-R7943. Na+-K+ pump activation inhibited EDR and [Ca2+]i increase (K+-induced inhibition of EDR and [Ca2+]i increase). The Na+-K+ pump inhibitor ouabain inhibited K+-induced inhibition of EDR. Monensin (>0.1 μM) and the NCX (forward and reverse mode) inhibitors 2′4′-dichlorobenzamil (>10 μM) or Ni2+ (>100 μM) inhibited K+-induced inhibition of EDR and [Ca2+]i increase. KB-R7943 did not inhibit K+-induced inhibition at up to 10 μM but did at 30 μM. In current-clamped MAECs, an increase in [K+]o from 6 to 12 mM depolarized the membrane potential, which was inhibited by ouabain, Ni2+, or KB-R7943. In aortic rings, the concentration of cGMP was significantly increased by acetylcholine and decreased on increasing [K+]o from 6 to 12 mM. This decrease in cGMP was significantly inhibited by pretreating with ouabain (100 μM), Ni2+ (300 μM), or KB-R7943 (30 μM). These results suggest that activation of the forward mode of NCX after Na+-K+ pump activation inhibits Ca2+ mobilization in endothelial cells, thereby modulating vasomotor tone.
7
Saini, Harjot K., Onkar N. Tripathi, Shetuan Zhang, Vijayan Elimban, and Naranjan S. Dhalla. "Involvement of Na+/Ca2+ exchanger in catecholamine-induced increase in intracellular calcium in cardiomyocytes." American Journal of Physiology-Heart and Circulatory Physiology 290, no. 1 (January 2006): H373—H380. http://dx.doi.org/10.1152/ajpheart.00613.2005.
Full textAbstract:
Although sarcolemmal (SL) Na+/Ca2+ exchanger is known to regulate the intracellular Ca2+ concentration ([Ca2+]i), its involvement in catecholamine-induced increase in [Ca2+]i is not fully understood. To gain some information in this regard, isolated rat cardiomyocytes were treated with different agents, which are known to modify Ca2+ movements, in the absence or presence of a β-adrenoceptor agonist, isoproterenol, and [Ca2+]i in cardiomyocytes was determined spectrofluorometrically with fura-2 AM. Treatment with isoproterenol did not alter [Ca2+]i in quiescent cardiomyocytes, whereas the ATP (purinergic receptor agonist)-induced increase in [Ca2+]i was significantly potentiated by isoproterenol. Unlike ryanodine and cyclopiazonic acid, which affect the sarcoplasmic reticulum function, SL L-type Ca2+ channel blockers verapamil and diltiazem, as well as a SL Ca2+-pump inhibitor, vanadate, caused a significant depression in the isoproterenol-induced increase in [Ca2+]i. The SL Na+/Ca2+ exchange blockers amiloride, Ni2+, and KB-R7943 also attenuated the isoproterenol-mediated increase in [Ca2+]i. Combination of KB-R7943 and verapamil showed additive inhibitory effects on the isoproterenol-induced increase in [Ca2+]i. The isoproterenol-induced increase in [Ca2+]i in KCl-depolarized cardiomyocytes was augmented by low Na+; this augmentation was significantly depressed by treatment with KB-R7943. The positive inotropic action of isoproterenol in isolated hearts was also reduced by KB-R7943. These data suggest that in addition to SL L-type Ca2+ channels, SL Na+/Ca2+ exchanger seems to play an important role in catecholamine-induced increase in [Ca2+]i in cardiomyocytes.
8
Amran, Md Shah, Nobuo Homma, and Keitaro Hashimoto. "Pharmacology of KB-R7943: A Na+-Ca2+ exchange inhibitor." Cardiovascular Drug Reviews 21, no. 4 (June 7, 2006): 255–76. http://dx.doi.org/10.1111/j.1527-3466.2003.tb00121.x.
Full text
9
Algara-Suárez, Paola, Catalina Romero-Méndez, Tom Chrones, Sergio Sánchez-Armass, Ulises Meza, Stephen M. Sims, and Ricardo Espinosa-Tanguma. "Functional coupling between the Na+/Ca2+ exchanger and nonselective cation channels during histamine stimulation in guinea pig tracheal smooth muscle." American Journal of Physiology-Lung Cellular and Molecular Physiology 293, no. 1 (July 2007): L191—L198. http://dx.doi.org/10.1152/ajplung.00485.2006.
Full textAbstract:
Airway smooth muscle (ASM) contracts partly due to an increase in cytosolic Ca2+. In this work, we found that the contraction caused by histamine depends on external Na+, possibly involving nonselective cationic channels (NSCC) and the Na+/Ca2+ exchanger (NCX). We performed various protocols using isometric force measurement of guinea pig tracheal rings stimulated by histamine. We observed that force reached 53 ± 1% of control during external Na+ substitution by N-methyl-d-glucamine+, whereas substitution by Li+ led to no significant change (91 ± 1%). Preincubation with KB-R7943 decreased the maximal force developed (52.3 ± 5.6%), whereas preincubation with nifedipine did not (89.7 ± 1.8%). Also, application of the nonspecific NCX blocker KB-R7943 and nifedipine on histamine-precontracted tracheal rings reduced force to 1 ± 3%, significantly different from nifedipine alone (49 ± 6%). Moreover, nonspecific NSCC inhibitors SKF-96365 and 2-aminoethyldiphenyl borate reduced force to 1 ± 1% and 19 ± 7%, respectively. Intracellular Ca2+ measurements in isolated ASM cells showed that KB-R7943 and SKF-96365 reduced the peak and sustained response to histamine (0.20 ± 0.1 and 0.19 ± 0.09 for KB-R, 0.43 ± 0.16 and 0.47 ± 0.18 for SKF, expressed as mean of differences). Moreover, Na+-free solution only inhibited the sustained response (0.54 ± 0.25). These data support an important role for NSCC and NCX during histamine stimulation. We speculate that histamine induces Na+ influx through NSCC that promotes the Ca2+ entry mode of NCX and CaV1.2 channel activation, thereby causing contraction.
10
Huang, Jingbo, Leif Hove-Madsen, and Glen F. Tibbits. "SR Ca2+ refilling upon depletion and SR Ca2+ uptake rates during development in rabbit ventricular myocytes." American Journal of Physiology-Cell Physiology 293, no. 6 (December 2007): C1906—C1915. http://dx.doi.org/10.1152/ajpcell.00241.2007.
Full textAbstract:
While it has been reported that a sparse sarcoplasmic reticulum (SR) and a low SR Ca2+ pump density exist at birth, we and others have recently shown that significant amounts of Ca2+ are stored in the neonatal rabbit heart SR. Here we try to determine developmental changes in SR Ca2+ loading mechanisms and Ca2+ pump efficacy in rabbit ventricular myocytes. SR Ca2+ loading (loadSR) and k0.5 (Ca2+ concentration at half-maximal SR Ca2+ uptake) were higher and lower, respectively, in younger age groups. Inhibition of the L-type calcium current ( ICa) with 15 μM nifedipine dramatically reduced loadSR in older but not in younger age groups. In contrast, subsequent inhibition of the Na+/Ca2+ exchanger (NCX) with 10 μM KB-R7943 strongly reduced loadSR in the younger but not the older age groups. Accordingly, the time integral of the inward NCX current (tail INCX) elicited on repolarization was highly sensitive to nifedipine in the older groups and sensitive to KB-R7943 in the younger groups. Interestingly, slow SR loading took place in the presence of both nifedipine and KB-R7943 in all age groups, although it was less prominent in the older groups. We conclude that the SR loading capacity at the earliest postnatal stages is at least as large as that of adult myocytes. However, reverse-mode NCX plays a prominent role in SR Ca2+ loading at early postnatal stages while ICa is the main source of SR Ca2+ loading at late postnatal and adult stages.
Dissertations / Theses on the topic "KB-R7943"
1
Zhao, Jun, and e52677@ems rmit edu au. "The functional study of Na+/Ca2+ exchanger in vascular smooth muscle cells." RMIT University. Medical Sciences, 2007. http://adt.lib.rmit.edu.au/adt/public/adt-VIT20080617.163746.
Full textAbstract:
Na+/Ca2+ exchanger (NCX) is a membrane protein which can mediate either Ca2+ entry (reverse mode) or exit (forward mode) in cells. As one of the major Ca2+ transport systems, NCX is postulated to play a critical role in the vascular smooth muscle cell. The aims of the present study are to firstly demonstrate the functional existence of NCX in vascular smooth muscle (including aorta and arteriole); to clarify the modulation of NCX; to explore the selectivity of NCX inhibitor KB-R7943; and lastly to investigate the role of NCX in the myogenic response. KB-R7943 has been widely used as a NCX inhibitor. The study investigated its pharmacological actions in rat aorta on a variety of Ca2+ dependent systems. Rat aortic rings were used. The constriction to low extracellular [Na+] is a functional response mediated by NCX operating in reverse mode. The data demonstrate that 10 µM KB-R7943 inhibited L-type Ca2+ channel, the capacitative Ca2+ entry and adrenergic receptor pathway. Nevertheless, KB-R7943 can be used as a selective inhibitor of NCX at the lower concentration of 1 µM in rat aortic rings. The study investigated whether the endothelium could modulate NCX in rat aortic rings. Lowering extracellular [Na+] to 1.18 mM induced constriction in endothelium denuded rat aortic rings, but only a small constriction in endothelium intact rat aortic rings. In endothelium intact rat aortic rings, the guanylate cyclise inhibitor ODQ (1 µM) and the nitric oxide synthase inhibitor L-NAME (50 µM) greatly amplified the vasoconstriction to lowering extracellular [Na+], but had no effect when the endothelium was removed. The adenylate cyclise inhibitor SQ 22536 (100 µM) and the cyclooxygenase inhibitor indomethacin (10 M) showed no significant effect on the low-Na+ induced vasoconstriction in either endothelium denuded or intact aortic rings. The results suggest that endothelium modulated the NCX operation via the nitric oxide/guanylate cyclase, not the adenylate cyclase system; further prostanoids including prostacyclin was not involved. The interaction between nitric oxide and NCX was furt her explored using the nitric oxide donor sodium nitroprusside. Endothelium denuded rat aortic rings were preconstricted to the same extent with either low Na+ (1.18 mM), or the thromboxane A2 agonist U46619 (0.1 µM) or high K+ (80 mM). The vasorelaxation of SNP (30 nM) in low Na+ constriction was significantly larger compared to other agents. This indicates that NO has a special antagonism of low Na+ constriction and a hypothesis is proposed involving Na+/K+ ATPase. The investigation of NCX is mainly conducted in large vessels; much less evidence is available for small resistance vessels. The study investigated the role of NCX on myogenic response in pressurized cremaster muscle arterioles. Reducing extracellular [Na+] resulted in graded vasoconstriction which was inhibited by NCX inhibitor SEA0400 (1 µM). Myogenic vasoconstriction and the concomitant rise in internal [Ca2+] were induced by a transmural pressure increase from 70 to 120 mmHg which was prevented by NCX inhibitor: SEA0400 (1 µM). In conclusion, the present study suggests that NCX contributes to the myogenic response in cremaster arteriole.
2
Elias, Chadwick Lee. "Inhibition of Na+-Ca2+ exchange by KB-R7943." 2002. http://hdl.handle.net/1993/18925.
Full text