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Статті в журналах з теми "Gastric vagal afferents"
1
Schwartz, G. J., T. H. Moran, W. O. White, and E. E. Ladenheim. "Relationships between gastric motility and gastric vagal afferent responses to CCK and GRP in rats differ." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 272, no. 6 (June 1, 1997): R1726—R1733. http://dx.doi.org/10.1152/ajpregu.1997.272.6.r1726.
Повний текст джерелаАнотація:
The brain-gut peptides cholecystokinin (CCK) and the mammalian bombesin-like peptide gastrin-releasing peptide (GRP) suppress food intake. Vagotomy blocks CCK- but not bombesin (BN)-induced feeding suppression, demonstrating differential vagal contributions. We examined the relationship between the ability of CCK and the active fragment of GRP, GRP-(18-27), to stimulate gastric vagal afferent activity and their ability to elicit changes in gastric motility. We also examined ligated cervical vagal segments and revealed specific 125I-CCK vagal binding without evidence of radiolabeled BN binding sites. Both close arterial and intraperitoneal CCK and GRP-(18-27) produced dose-dependent increases in activity in gastric vagal mechanoreceptive afferents. CCK dose dependently decreased gastric pressure without altering antral wall tension, whereas GRP-(18-27) dose dependently increased both gastric pressure and peak antral wall muscle tension. These results suggest that GRP-(18-27) activates gastric vagal afferents secondary to its stimulation of gastric motor effects. CCK activates this same population of vagal afferents independent of changes in gastric tension, suggesting a direct action of CCK at functional vagal CCK receptors.
2
van de Wall, E. H. E. M., P. Duffy, and R. C. Ritter. "CCK enhances response to gastric distension by acting on capsaicin-insensitive vagal afferents." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 289, no. 3 (September 2005): R695—R703. http://dx.doi.org/10.1152/ajpregu.00809.2004.
Повний текст джерелаАнотація:
Capsaicin treatment destroys vagal afferent C fibers and markedly attenuates reduction of food intake and induction of hindbrain Fos expression by CCK. However, both anatomical and electrophysiological data indicate that some gastric vagal afferents are not destroyed by capsaicin. Because CCK enhances behavioral and electrophysiological responses to gastric distension in rats and people, we hypothesized that CCK might enhance the vagal afferent response to gastric distension via an action on capsaicin-insensitive vagal afferents. To test this hypothesis, we quantified expression of Fos-like immunoreactivity (Fos) in the dorsal vagal complex (DVC) of capsaicin-treated (Cap) and control rats (Veh), following gastric balloon distension alone and in combination with CCK injection. In Veh rats, intraperitoneal CCK significantly increased DVC Fos, especially in nucleus of the solitary tract (NTS), whereas in Cap rats, CCK did not significantly increase DVC Fos. In contrast to CCK, gastric distension did significantly increase Fos expression in the NTS of both Veh and Cap rats, although distension-induced Fos was attenuated in Cap rats. When CCK was administered during gastric distension, it significantly enhanced NTS Fos expression in response to distension in Cap rats. Furthermore, CCK's enhancement of distension-induced Fos in Cap rats was reversed by the selective CCK-A receptor antagonist lorglumide. We conclude that CCK directly activates capsaicin-sensitive C-type vagal afferents. However, in capsaicin-resistant A-type afferents, CCK's principal action may be facilitation of responses to gastric distension.
3
Raybould, Helen E., Jorg Glatzle, Carla Robin, James H. Meyer, Thomas Phan, Helen Wong, and Catia Sternini. "Expression of 5-HT3 receptors by extrinsic duodenal afferents contribute to intestinal inhibition of gastric emptying." American Journal of Physiology-Gastrointestinal and Liver Physiology 284, no. 3 (March 1, 2003): G367—G372. http://dx.doi.org/10.1152/ajpgi.00292.2001.
Повний текст джерелаАнотація:
Intestinal perfusion with carbohydrates inhibits gastric emptying via vagal and spinal capsaicin-sensitive afferent pathways. The aim of the present study was to determine the role of 1) 5-hydroxytryptamine (5-HT)3receptors (5-HT3R) in mediating glucose-induced inhibition of gastric emptying and 2) 5-HT3R expression in vagal and spinal afferents in innervating the duodenum. In awake rats fitted with gastric and duodenal cannulas, perfusion of the duodenum with glucose (50 and 100 mg) inhibited gastric emptying. Intestinal perfusion of mannitol inhibited gastric emptying only at the highest concentration (990 mosm/kgH2O). Pretreatment with the 5-HT3R antagonist tropisetron abolished both glucose- and mannitol-induced inhibition of gastric emptying. Retrograde labeling of visceral afferents by injection of dextran-conjugated Texas Red into the duodenal wall was used to identify extrinsic primary afferents. Immunoreactivity for 5-HT3R, visualized with an antibody directed to the COOH terminus of the rat 5-HT3R, was found in >80% of duodenal vagal and spinal afferents. These results show that duodenal extrinsic afferents express 5-HT3R and that the receptor mediates specific glucose-induced inhibition of gastric emptying. These findings support the hypothesis that enterochromaffin cells in the intestinal mucosa release 5-HT in response to glucose, which activates 5-HT3R on afferent nerve terminals to evoke reflex changes in gastric motility. The primary glucose sensors of the intestine may be mucosal enterochromaffin cells.
4
Smid, Scott D., Richard L. Young, Nicole J. Cooper, and L. Ashley Blackshaw. "GABABR expressed on vagal afferent neurones inhibit gastric mechanosensitivity in ferret proximal stomach." American Journal of Physiology-Gastrointestinal and Liver Physiology 281, no. 6 (December 1, 2001): G1494—G1501. http://dx.doi.org/10.1152/ajpgi.2001.281.6.g1494.
Повний текст джерелаАнотація:
GABAB-receptor (GABABR) agonists reduce transient lower esophageal sphincter relaxation (TLESR) and reflux episodes through an action on vagal pathways. In this study, we determined whether GABABR are expressed on vagal afferent neurones and whether they modulate distension-evoked discharge of vagal afferents in the isolated stomach. Vagal mehanoreceptor activity was recorded following distensions of the isolated ferret proximal stomach before and after perfusion with the GABABR-selective agonists baclofen and 3-aminopropylphosphinic acid (3-APPiA). Retrograde labeling and immunohistochemistry were used to identify GABABR located on vagal afferent neurones in the nodose ganglia. Vagal afferent fibers responded to isovolumetric gastric distension with an increase in discharge. The GABAB-receptor agonists baclofen (5 × 10−5 M) and 3-APPiA (10−6 to 10−5 M) but not muscimol (GABAA-selective agonist: 1.3 × 10−5 M) significantly decreased afferent distension-response curves. The effect of baclofen (5 × 10−5 M) was reversed by the GABAB-receptor antagonist CGP 62349 (10−5 M). Over 93% of retrogradely labeled gastric vagal afferents in the nodose ganglia expressed immunoreactivity for the GABABR. GABABR expressed on vagal afferent fibers directly inhibit gastric mechanosensory activity. This is likely a contributing mechanism to the efficacy of GABAB-receptor agonists in reducing TLESR and reflux episodes in vivo.
5
Mathis, Carole, Timothy H. Moran, and Gary J. Schwartz. "Load-sensitive rat gastric vagal afferents encode volume but not gastric nutrients." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 274, no. 2 (February 1, 1998): R280—R286. http://dx.doi.org/10.1152/ajpregu.1998.274.2.r280.
Повний текст джерелаАнотація:
To assess nutrient sensitivity in a population of gastric load-sensitive vagal afferents, their neurophysiological activity was examined in anesthetized rats with inflated pyloric cuffs after gastric infusion of a range of volumes of nutrient and equiosmotic saline solutions. Responses to physiological saline loads (1, 2, 4, and 8 ml) were compared with responses elicited by the same volume range of carbohydrate (12.5% glucose), protein (12.5% peptone), and equiosmotic hypertonic (750 mosM) saline. The threshold load volume of physiological saline required to increase gastric vagal afferent activity was 1 ml. Thereafter, there was a dose-dependent relationship between increasing gastric volume and firing rate and between gastric volume and pressure. The dose-response relationships elicited by glucose, peptone, and equiosmotic hypertonic saline loads did not differ from those elicited by physiological saline loads. These data identify a population of gastric load-sensitive vagal afferents unresponsive to the chemical composition of gastric contents and are consistent with a role for vagal gastric volume signals but not gastric nutrient content in the negative feedback control of ingestion.
6
Kang, Yu-Ming, Klaus Bielefeldt, and G. F. Gebhart. "Sensitization of Mechanosensitive Gastric Vagal Afferent Fibers in the Rat by Thermal and Chemical Stimuli and Gastric Ulcers." Journal of Neurophysiology 91, no. 5 (May 2004): 1981–89. http://dx.doi.org/10.1152/jn.01097.2003.
Повний текст джерелаАнотація:
In the present study we examined the effects of acute thermal and chemical stimuli and gastric ulceration on mechanosensitive gastric vagal afferent fibers. Single-fiber recordings were made from the cervical vagus nerve. Mechanosensitive afferent fibers were identified by response to gastric distension (GD). Intragastric pressure was maintained below 3 mmHg during intragastric instillation of saline, heated saline, HCl, or glycocholic acid. Responses to graded GD (5–60 mmHg, 20 s, 4-min interval) were determined before and after 30-min exposure to thermal or chemical stimuli. All mechanosensitive fibers studied were C-fibers (mean CV: 1.07 ± 0.07 m/s). Saline (37°C) did not affect resting activity or alter responses to GD, but exposure to heated saline (46°C) significantly increased resting activity and sensitized responses to GD. The decrease in resting activity was hydrochloric acid concentration dependent (0.025–0.2 N), but responses to GD were sensitized after 30-min exposure to 0.1 N HCl ( n = 7). The bile acid glycocholic acid significantly increased resting activity and desensitized responses to GD at an intragastric pH of 7, and similarly increased resting activity but sensitized responses to GD ( n = 6) at an intragastric pH of 1.2. Vagal afferents recorded in rats with gastric ulcers had significantly greater resting activity and responses to GD than sham ulcer rats; intragastric instillation of glycocholic acid (pH 1.2) further increased afferent fiber excitability. These findings indicate that acute gastric thermal and chemical stimuli alter the response characteristics of mechanosensitive vagal afferents in the absence of inflammation or structural damage. Accordingly, acute sensitization of gastric afferents through different stimulus modalities may contribute to the development of dyspeptic symptoms. In the presence of gastric inflammation, mechanosensitive vagal afferents exhibit a further increase in excitability.
7
Young, Richard L., Amanda J. Page, Tracey A. O'Donnell, Nicole J. Cooper, and L. Ashley Blackshaw. "Peripheral versus central modulation of gastric vagal pathways by metabotropic glutamate receptor 5." American Journal of Physiology-Gastrointestinal and Liver Physiology 292, no. 2 (February 2007): G501—G511. http://dx.doi.org/10.1152/ajpgi.00353.2006.
Повний текст джерелаАнотація:
Metabotropic glutamate receptors (mGluR) are classified into group I, II, and III mGluR. Group I (mGluR1, mGluR5) are excitatory, whereas group II and III are inhibitory. mGluR5 antagonism potently reduces triggering of transient lower esophageal sphincter relaxations and gastroesophageal reflux. Transient lower esophageal sphincter relaxations are mediated via a vagal pathway and initiated by distension of the proximal stomach. Here, we determined the site of action of mGluR5 in gastric vagal pathways by investigating peripheral responses of ferret gastroesophageal vagal afferents to graded mechanical stimuli in vitro and central responses of nucleus tractus solitarius (NTS) neurons with gastric input in vivo in the presence or absence of the mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP). mGluR5 were also identified immunohistochemically in the nodose ganglia and NTS after extrinsic vagal inputs had been traced from the proximal stomach. Gastroesophageal vagal afferents were classified as mucosal, tension, or tension-mucosal (TM) receptors. MPEP (1–10 μM) inhibited responses to circumferential tension of tension and TM receptors. Responses to mucosal stroking of mucosal and TM receptors were unaffected. MPEP (0.001–10 nmol icv) had no major effect on the majority of NTS neurons excited by gastric distension or on NTS neurons inhibited by distension. mGluR5 labeling was abundant in gastric vagal afferent neurons and sparse in fibers within NTS vagal subnuclei. We conclude that mGluR5 play a prominent role at gastroesophageal vagal afferent endings but a minor role in central gastric vagal pathways. Peripheral mGluR5 may prove a suitable target for reducing mechanosensory input from the periphery, for therapeutic benefit.
8
Schwartz, Gary J., and Timothy H. Moran. "Duodenal nutrient exposure elicits nutrient-specific gut motility and vagal afferent signals in rat." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 274, no. 5 (May 1, 1998): R1236—R1242. http://dx.doi.org/10.1152/ajpregu.1998.274.5.r1236.
Повний текст джерелаАнотація:
Volume and chemical characteristics of meals in the gut have been proposed to generate vagal afferent signals that mediate the negative feedback control of ingestion and gastric emptying. Furthermore, duodenal nutrients elicit changes in gastrointestinal motility that may stimulate mechanosensitive vagal afferents. The degree to which the activity of an individual vagal afferent fiber can be modified by both mechanical and nutrient properties in the gut remains unclear. The present studies evaluated the relationships between distal antral and proximal duodenal load-sensitive vagal afferent activity and gastroduodenal motility in response to duodenal nutrient exposure in ketamine-xylazine-anesthetized rats. Duodenal carbohydrate (glucose) and amino acid (peptone) infusions (0.2 ml/min, 0.2–0.5 kcal/ml) stimulated concentration-dependent increases in 1) antroduodenal contractions and 2) antral and duodenal vagal afferent activity beyond those attributable to osmolarity alone. In addition, duodenal peptone was more effective than equicaloric glucose in eliciting this vagal activity. These data demonstrate that the proximal duodenum can discriminate its nutrient chemical contents and that gastroduodenal load-sensitive vagal afferents indirectly transduce nutrient chemical information.
9
Schwartz, G. J., P. R. McHugh, and T. H. Moran. "Pharmacological dissociation of responses to CCK and gastric loads in rat mechanosensitive vagal afferents." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 267, no. 1 (July 1, 1994): R303—R308. http://dx.doi.org/10.1152/ajpregu.1994.267.1.r303.
Повний текст джерелаАнотація:
To identify the transduction mechanisms underlying gastric vagal afferent responses to gastric loads and cholecystokinin (CCK), we investigated the ability of specific CCK antagonists, acute pylorectomy, and cholinergic blockade to effect these vagal afferent responses. The CCK-B antagonist L-365,260 (10 pmol-1 nmol) failed to block the gastric vagal afferent response to gastric loads or 100 pmol CCK, while the CCK-A antagonist devazepide (100 pmol-100 nmol) competitively and dose dependently attenuated the response to CCK but not to gastric loads. Application of 100 nmol of the low-affinity CCK receptor antagonist CCK-JMV-180 also completely blocked the gastric vagal afferent response to 100 pmol CCK. Acute pylorectomy failed to block the gastric vagal afferent response to 100 pmol CCK or 2-ml gastric loads. Atropine sulfate administration (15 mg/rat) failed to block the gastric vagal afferent response to 100 pmol CCK or 2-ml gastric loads. These data suggest that 1) the vagal afferent response to CCK is mediated through CCK's interactions with vagal, rather than pyloric, CCK-A receptors, and 2) the vagal afferent responses to CCK and to gastric loads are mediated by dissociable, possibly independent, transduction mechanisms.
10
Danzer, Marion, Milana Jocic, Claudia Samberger, Evelin Painsipp, Elisabeth Bock, Maria-Anna Pabst, Karl Crailsheim, Rudolf Schicho, Irmgard T. Lippe, and Peter Holzer. "Stomach-brain communication by vagal afferents in response to luminal acid backdiffusion, gastrin, and gastric acid secretion." American Journal of Physiology-Gastrointestinal and Liver Physiology 286, no. 3 (March 2004): G403—G411. http://dx.doi.org/10.1152/ajpgi.00308.2003.
Повний текст джерелаАнотація:
Vagal afferents play a role in gut-brain signaling of physiological and pathological stimuli. Here, we investigated how backdiffusion of luminal HCl or NH4OH and pentagastrin-stimulated acid secretion interact in the communication between rat stomach and brain stem. Rats were pretreated intraperitoneally with vehicle or appropriate doses of cimetidine, omeprazole, pentagastrin, dexloxiglumide (CCK1 receptor antagonist), and itriglumide (CCK2 receptor antagonist) before intragastric administration of saline or backdiffusing concentrations of HCl or NH4OH. Two hours later, neuronal activation in the nucleus of the solitary tract (NTS) and area postrema was visualized by c-Fos immunohistochemistry. Exposure of the rat gastric mucosa to HCl (0.15-0.5 M) or NH4OH (0.1-0.3 M) led to a concentration-dependent expression of c-Fos in the NTS, which was not related to gender, gastric mucosal injury, or gastropyloric motor alterations. The c-Fos response to HCl was diminished by cimetidine and omeprazole, enhanced by pentagastrin, and left unchanged by dexloxiglumide and itriglumide. Pentagastrin alone caused an omeprazole-resistant expression of c-fos, which in the NTS was attenuated by itriglumide and prevented by dexloxiglumide but in the area postrema was reduced by dexloxiglumide and abolished by itriglumide. We conclude that vagal afferents transmit physiological stimuli (gastrin) and pathological events (backdiffusion of luminal HCl or NH4OH) from the stomach to the brain stem. These communication modalities interact because, firstly, acid secretion enhances afferent signaling of gastric acid backdiffusion and, secondly, gastrin activates NTS neurons through stimulation of CCK1 receptors on vagal afferents and of CCK2 receptors on area postrema neurons projecting to the NTS.
Дисертації з теми "Gastric vagal afferents"
1
Christie, Stewart David. "Endocannabinoid regulation of gastric vagal afferent signalling." Thesis, 2020. http://hdl.handle.net/2440/126014.
Повний текст джерелаАнотація:
Background: Gastric vagal afferents (GVAs) play a role in peripheral appetite control. Tension sensitive GVAs respond to stretch or distension of the stomach sending signals to the hindbrain to produce feelings of fullness and satiety. The sensitivity of tension sensitive GVAs is reduced in diet-induced obesity which may contribute to increased meal size. Further, transient receptor potential vanilloid 1 (TRPV1) knockout mice also show decreased GVA tension receptor sensitivity. Endocannabinoids (ECs) regulate appetite via cannabinoid 1 (CB1) receptors and are also endogenous ligands for TRPV1. The CB1 receptor and TRPV1 are expressed on GVAs and the CB1 receptor is also expressed on gastric ghrelin cells. Further, the endocannabinoid anandamide (AEA; ligand for CB1) is expressed in the stomach. However, it is not known if ECs, ghrelin, and TRPV1 interact to regulate GVA sensitivity. Aims: To determine in lean and diet induced obese mice: 1. The co-expression of CB1, TRPV1, and ghrelin receptor (growth hormone secretagogue receptor; GHSR) in individual GVA cell bodies. 2. The effect of AEA on GVA sensitivity and secondary messenger pathways involved. 3. The effect of AEA and ghrelin on the expression of orexigenic receptors in nodose ganglia. Methods: Retrograde tracing was used to identify single GVA cell bodies in the nodose ganglia which was then combined with single cell QRT-PCR. An in vitro electrophysiology preparation was used to determine the effects of methanandamide (mAEA; stable analogue of AEA) on the sensitivity of GVAs in C57BL/6 mice fed ad libitum with either a standard laboratory diet (SLD) or high fat diet (HFD). This was performed with mAEA alone or in combination with antagonists to determine possible secondary messenger pathways. Nodose ganglia were cultured for 14 hours in a medium containing mAEA or ghrelin and then analysed via QRT-PCR for changes in receptor or ion channel expression. Results: CB1, TRPV1, and GHSR were expressed and co-expressed in individual tension sensitive GVA neurons in a diet-dependent manner. In SLD-mice mAEA exhibited concentration-dependent dual inhibitory and excitatory effects on the mechanosensitivity of tension sensitive GVAs. This was abolished to a single inhibitory effect regardless of concentration in HFD-mice. In cultured vagal afferent cell bodies, exposure to mAEA and ghrelin altered the expression of CB1, TRPV1, and GHSR mRNA in a diet dependent manner. Conclusions: ECs, acting through CB1 and TRPV1, have a pivotal role in modulating GVA satiety signals depending on the second messenger pathway utilised. In HFD-mice only an inhibitory effect is observed. These changes may contribute to the development and/or maintenance of obesity.Thesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 2020
2
Kentish, Stephen James. "Obesity induced dysfunction of gastric vagal afferent signalling." Thesis, 2013. http://hdl.handle.net/2440/82617.
Повний текст джерелаАнотація:
Background: The stomach has the ability to respond to chemical and mechanical stimuli to mediate satiety through vagal pathways. Within the stomach specialised endocrine and epithelial cells synthesise and secrete leptin and ghrelin, which influence food intake through vagal afferent pathways. However, it remains to be determined if mechanosensitive gastric vagal afferent signalling is disrupted in obesity and whether this may play a role in the overconsumption of energy required for the maintenance of diet induced obesity. Furthermore, whether leptin can modulate mechanically sensitive gastric vagal afferents and whether any ability of leptin and ghrelin to modulate mechanically sensitive endings is altered in obesity has not been conclusively determined. Aims: To determine in lean mice and in high fat diet induced obese mice: 1) The effect of gastric peptides ghrelin and leptin on gastric vagal afferent mechanosensitivity. 2) The effect of gastric peptides on the expression of their own and other peptide receptors. 3) The reversibility of diet-induced obesity. Methods: Lean and diet-induced obese mice were created by feeding 8 week old female C57BL/6 mice a standard chow diet (N=4-20; 7% energy from fat) or a high-fat diet (N=4-20; 60% of energy from fat) respectively. An in vitro gastro-oesophageal vagal flat sheet preparation was utilised to determine the mechanosensitivity of vagal afferent endings and the effect of leptin, ghrelin and diet-induced obesity on this mechanosensitivity. Messenger RNA (mRNA) content in nodose ganglia was measured by QRT-PCR. Specific gastric vagal afferent cell bodies were identified by retrograde labelling and this technique was combined with QRT-PCR to determine mRNA content in specific gastric cell bodies. Anterograde tracing by injection of tracer into the nodose ganglia allowed visualisation of the distribution of gastric vagal afferents in relation to leptin and ghrelin positive cells. Nodose ganglia were cultured overnight in medium containing leptin, ghrelin or neuropeptide W (NPW) followed by QRTPCR to determine any homologous or heterologous receptor expression regulation. Results: Diet-induced obesity caused a reduction in the mechanosensitivity of gastric tension receptors. Furthermore, it increased the inhibitory effect of ghrelin on gastric vagal afferent mechanosensitivity and resulted in a switch in the effect of leptin from potentiating to inhibitory. The gut peptides leptin, ghrelin and NPW modified the mRNA content of their own and each other‘s receptors in a manner that was dependent on dietary group. Placing obese mice back on a chow diet resulted in an initial weight loss but subsequent increased food consumption and weight gain. The decrease in mechanosensitivity caused by the high fat diet was not reversible by placing diet-induced obese mice back on a chow diet and the effects of leptin were only partially reversed. Conclusions: Vagal afferent function is altered in diet-induced obesity to the extent that both the baseline response and the effects of leptin and ghrelin may act to facilitate increased food intake. Given the lack of reversibility of changes observed in diet-induced obesity this suggests that gastric vagal afferents may play a role in the maintenance of obesity and may act to oppose weight loss.Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 2013
3
Slattery, James Arthur. "Modulation of mechanosensitive gastro-oesophageal vagal afferents by novel targets." Thesis, 2011. http://hdl.handle.net/2440/69568.
Повний текст джерелаАнотація:
Modulation of signals from peripheral vagal afferent mechanoreceptors to the central nervous system has been identified as the most accessible target for control of neuronal pathways and reflexes central to gastrointestinal disorders such as GORD, disordered food intake and functional dyspepsia. There are numerous candidates for modulation of vagal afferent signals from the gastrointestinal tract to the CNS, all of which may represent novel targets for therapeutic treatment of gastrointestinal disorders. These candidates include excitatory ionotropic receptors as well as inhibitory and excitatory (metabotropic) G-protein coupled receptors. Four were chosen for study in this thesis. These are:
1) Galanin receptors, which may be excitatory or inhibitory GPCRs depending on their subtype
2) Excitatory ionotropic glutamate receptors, and their relative contribution compared with excitatory metabotropic glutamate receptors.
3) Ghrelin receptors, which may have excitatory or inhibitory actions on nerves elsewhere.
Aims
Determine the roles of four groups of identified receptors in modulation of mechanosensitivity of peripheral gastro-oesophageal mechanoreceptors and to identify endogenous ligands and receptors in vagal cell bodies to complement their known location in stomach.
Methods:
Novel in vitro mouse and ferret vagal gastro-oesophageal preparations have been previously reported. Accurate quantification of mechanical responses was performed according to the primary stimulus for the type of afferent. Mechanical
sensitivity of primary afferents was established by mechanical stimulation of the preparation via circumferential tension (0.5-7g) or mucosal stroking with von Frey hairs (10-1000mg). Afferent responses to mechanical stimulus were tested in the presence of selective agonists and antagonists of galanin, ionotropic and metabotropic glutamate as well as ghrelin receptors. In additional studies, the effects of galanin and selective receptor agonists and antagonist on GalR1 wild type (+/+) and null mutant (-/-) mice were determined.
Results:
Two types of vagal afferent mechanoreceptors were identified in the mouse model, decribed as tension and mucosal sensitive afferents. An additional sub-type, tensionmucosal was identified in the ferret oesophagus.
1) Galanin induced potent inhibition of mechanosensitivity of both types of mouse afferent, an effect mimicked by a GalR1/2 agonist but was absent in null mutant GalR1 (-/-) mice. A GalR1/2 agonist demonstrated minor potentiation of mechanosensitivity in null mutant GalR1 (-/-) mice. There was no significant effect of GalR3 selective ligands observed however.
2) Selective iGluR receptor agonists AMPA and NMDA dose dependently potentiated responses of vagal afferents to mechanical sensitivity, an effect reversed by both selective and non-selective antagonists, whilst the mGluR5 antagonist MTEP concentration dependently inhibited mechanosensitivity. Efficacy of agonists and antagonists for the various receptor sub-types differed between mucosal and tension receptors. No role for Kainate receptors was observed in this study.
3) In a mouse model ghrelin significantly reduced the response of tension sensitive afferents to circumferential tension, an effect reversed by a selective receptor antagonist. This effect was not observed in mouse mucosal receptors. In the ferret model, ghrelin significantly reduced the response of mucosal and tension mucosal receptors to mucosal stroking however did not affect responses to circumferential tension.
Conclusions:
The current study highlights the complex interaction between excitatory and inhibitory receptors, located on peripheral vagal afferent terminals, that serve to modulate afferent signalling to the CNS and thus allows precise control over gut reflex and secretory function. This study further adds to an expanding list of modulators of peripheral vagal afferent mechanoreceptors, providing additional possible novel therapeutic candidates for treatment of upper gastro-intestinal dysfunction.Thesis (Ph.D.) -- University of Adelaide, School of Medical Sciences, 2011
Частини книг з теми "Gastric vagal afferents"
1
Raybould, Helen E., Peter Holzer, Gerard Thiefin, Helge H. Holzer, Masashi Yoneda, and Yvette F. Tache. "Vagal Afferent Innervation and Regulation of Gastric Function." In Advances in Experimental Medicine and Biology, 109–27. Boston, MA: Springer US, 1991. http://dx.doi.org/10.1007/978-1-4899-0744-8_10.
Повний текст джерела
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Rogers, R. C., and G. E. Hermann. "Central Regulation of Brainstem Gastric Vago-Vagal Control Circuits." In Neuroanatomy and Physiology of Abdominal Vagal Afferents, 99–134. CRC Press, 2020. http://dx.doi.org/10.1201/9781003069171-5.
Повний текст джерела
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Raybould, H. E. "Vagal Afferent Innervation and the Regulation of Gastric Motor Function." In Neuroanatomy and Physiology of Abdominal Vagal Afferents, 193–219. CRC Press, 2020. http://dx.doi.org/10.1201/9781003069171-9.
Повний текст джерела
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Niijima, Akira. "Chapter 17 The effect of gastro-entero-pancreatic hormones on the activity of vagal hepatic afferent fibres." In Progress in Brain Research, 155–60. Elsevier, 1988. http://dx.doi.org/10.1016/s0079-6123(08)63009-5.
Повний текст джерела