Bethanechol-stimulated Gastric Acid Research Articles

Inhibition of gastric acid secretion by Ya-hom in isolated mouse whole stomach

Background: Ya-hom, the traditional Thai formula for abdominal discomfort treatment has, been reported to inhibit gastric acid secretion in gastric fistula rats. However, the mechanism underlying its action remains unclear. Objective: To investigate the gastric acid inhibitory action of Ya-hom and its mechanism of action by using an isolated mouse whole stomach model. Methods: The gastric acid secretion of isolated mouse whole stomach was stimulated by histamine (5.0 μM) or bethanechol (10 or 100 μM) after adding the inhibitors (atropine 1 μM, ranitidine 10 μM, indomethacin 0.1 μM or L-NAME 300 μM) and/or Ya-hom to the serosal solution. The effluent perfusate was collected continuously in 10-minute fractions for 120 minutes after stimulation. Results: Re-dissolved lyophilized Ya-hom extract at doses of 2.5, 5.0, 10.0, and 20.0 mg/mL inhibited histaminestimulated gastric acid secretion in a dose-dependent manner. Inhibition of Ya-hom (10 mg/mL) was also observed in the presence of atropine (1 μM), which was used to eliminate effects of endogenous acetylcholine. Ya-hom inhibited bethanechol-stimulated gastric acid secretion in the presence and absence of ranitidine. While the inhibitory action of Ya-hom on histamine-stimulated gastric secretion was not affected by indomethacin, it was attenuated by concomitant treatment with the nitric oxide synthase inhibitor (L-NAME). Conclusion: Ya-hom did not stimulate gastric acid secretion in the isolated mouse whole stomach. Ya-hom significantly inhibited gastric acid secretion after this was stimulated via histamine or bethanechol. Nitric oxide stimulation plays an important role in the inhibitory action of Ya-hom.

The acetone soluble fraction from bark extract of Stryphnodendron adstringens (Mart.) coville inhibits gastric acid secretion and experimental gastric ulceration in rats.

The acetone soluble fraction from a crude methanol extract of Stryphnodendron adstringens stem bark (AFSAB) was evaluated in acute (ethanol, indomethacin and hypothermic restraint-stress) and chronic (acetic acid) models of gastric ulceration and on basal and bethanechol-stimulated gastric acid secretion in rats. Rats pretreated orally with AFSAB at doses of 400 and 800 mg/kg showed significant decreases of gastric lesion scores in ethanol (62% and 98%) and hypothermic restraint-stress (89% and 88%) models but exerted no significant influence on indomethacin-induced acute or acetic acid-induced chronic ulceration. In pylorus-ligated rats, AFSAB significantly decreased the basal as well as bethanechol-stimulated gastric secretory volume and the total acidity with an elevated pH value. AFSAB failed to modify the gastric mucus and the gastric wall nonprotein-sulphydryl content. These results point to a possible antisecretory effect of AFSAB which account for the observed antiulcer activity in ethanol and hypothermic restraint-stress induced models of acute gastric ulceration.

Inhibitory action of galanin on gastric acid secretion in pentobarbital-anesthetized rats

The effects of galanin and two galanin fragments, GAL(9–29) and GAL(15–29), were studied for potential effects on pentagastrin- and bethanechol-stimulated gastric acid secretion in a pentobarbital-anesthetized rat experimental model. At a dose of 10 μg/kg/h, galanin potently inhibited pentagastrin-stimulated gastric acid secretion whereas inhibition of bethanechol-stimulated gastric acid secretion was not statistically significant. Simultaneous iv infusion of galanin and atropine did not affect the inhibitory action of the former. In similar experiments, a GAL(15–29) fragment was completely inactive whilst GAL(9–29) retained only about 5% potency. These results indicate that galanin probably induces its inhibitory effects by acting directly on the parietal cells rather than through a cholinergic pathway. They also demonstrate that the rat gastric acid inhibitory activity of galanin depends critically on the integrity of the first fourteen N-terminal amino acids.

An analysis of the effects of galanin on gastric acid secretion and plasma levels of gastrin in the dog

The effects of galanin on gastric acid secretion and plasma levels of gastrin were studied in conscious dogs chronically fitted with gastric fistulas. Continuous i.v. infusion of galanin (2 μg · kg −1 · h −) for 2 h did not affect unstimulated total acid output or plasma levels of gastrin. In contrast, simultaneous i.v. infusion of galanin (1–2 μg · kg −1 · h −1) inhibited the bombesin-stimulated output of acid whereas the effects of bombesin on gastrin output were not significantly modified. Galanin (2–4 μg · kg −1 i.v.) also depressed the secretory response to 2-deoxy-D-glucose without significantly affecting plasma gastrin levels. Galanin (2–4 μg · kg −1 i.v.) did not depress bethanechol-stimulated gastric acid output or inhibit histamine-stimulated gastric acid secretion. These findings indicate that galanin inhibits the bombesin- and 2-deoxy-D-glucose-stimulated secretion of gastric acid in conscious dogs by an action which is probably exerted at the level of the cholinergic nerve terminals.

Antiulcerogenic and antisecretory effects of a novel diphenylmethane derivative and antiestrogen binding site ligand.

N,N-Diethyl-2-[4-(phenylmethyl)-phenoxy]-ethanamine hydrochloride (DPPE) is a para-diphenylmethane derivative that binds selectively and with high affinity to the microsomal antiestrogen binding site (AEBS). Recent studies with DPPE indicate that AEBS is closely related to a lower affinity non-H1, non-H2 histamine site that may be associated with calcium channels; the DPPE-AEBS site is different from that which verapamil binds, however, DPPE, but not verapamil, demonstrates antiproliferative effects in vitro and is antiestrogenic in vivo. We now show that DPPE profoundly inhibits restraint and cold stress and ethanol-induced gastric ulcer formation, accelerates ulcer healing, attenuates the stress-induced rise in plasma corticosterone level, and significantly reduces basal and H2 agonist (dimaprit)-stimulated and, to a lesser extent, bethanechol-stimulated gastric acid output in conscious rats. A nonulcerogenic but prostaglandin-depleting dose of indomethacin completely blocks the inhibitory effects of DPPE on stress ulcer formation. Conversely, verapamil only slightly attenuates dimaprit-stimulated gastric acid secretion and exacerbates ethanol-induced gastric ulcers; its anti-stress ulcer effects are only partially attenuated by indomethacin. These findings support the likelihood that the site of action of DPPE is different from that of verapamil, and that an effect on prostaglandins may, at least in part, contribute to its antiulcer and apparent cytoprotective effects.

Inhibitory action of peptide YY on gastric acid secretion.

The purpose of this study is to investigate the effect of peptide YY (PYY) on pentagastrin-, histamine-, and bethanechol-stimulated gastric acid secretion and the possible mechanisms by which PYY inhibits gastric acid secretion. Six mongrel dogs with chronic gastric and duodenal fistulas were given an intravenous infusion of pentagastrin (0.5 microgram . kg-1 . h-1), histamine (18 micrograms . kg-1 . h-1), or bethanechol (80 micrograms . kg-1 . h-1) either alone or simultaneously with intravenous PYY (100, 200, 400, pmol . kg-1 . h-1). PYY (100, 200, 400 pmol . kg-1 . h-1) inhibited pentagastrin-stimulated gastric acid secretion in a dose-dependent manner. PYY (400 pmol . kg-1 . h-1) did not depress bethanechol-stimulated gastric acid secretion. PYY (400 pmol . kg-1 . h-1) also failed to inhibit histamine-stimulated gastric acid secretion. Furthermore, PYY inhibit pentagastrin-stimulated gastric acid secretion in the face of atropine, vagotomy, or indomethacin treatment. These findings indicate that the inhibitory action of PYY on gastric acid secretion is in part independent of long and short cholinergic pathways. These findings also indicate that the inhibitory mechanism of PYY is independent of prostaglandin synthesis. Our findings are discussed in relation to previous reports regarding the effects of PYY on gastric acid secretion.

Effect of Peptide YY on Cephalic, Gastric, and Intestinal Phases of Gastric Acid Secretion and on the Release of Gastrointestinal Hormones

The objective of this study was to investigate the effects of a novel gut peptide, peptide YY (PYY), on the cephalic, gastric, and intestinal phases of gastric acid secretion and to explore the mechanisms involved. The cephalic phase of gastric acid secretion, stimulated by the intravenous injection of 2-deoxyglucose (75 mg/kg), was found to be inhibited by intravenous PYY (100, 200, 400 pmol/kg X h) in a dose-related fashion. Peptide YY (200 and 400 pmol/kg X h) also resulted in a significant dose-dependent inhibition of the gastric phase of acid secretion. On the other hand, PYY (400 pmol/kg X h) failed to affect the intestinal phase of gastric acid output. Serum gastrin levels were increased on infusion of 10% liver extract into stomach, but were unaffected on instillation of liver extract into duodenum. Peptide YY did not inhibit the release of gastrin in either the gastric or intestinal phase studies. Furthermore, PYY had no significant effect on either the basal release of secretin, gastric inhibitory polypeptide, pancreatic polypeptide, or neurotensin, or on the stimulated release of pancreatic polypeptide by 2-deoxyglucose. The specific binding of gastrin to its receptors on the fundic mucosa was also unaffected by PYY. These results indicate that PYY inhibits the cephalic and gastric phases of acid secretion independently, and that its actions are not mediated by either a negative effect on gastrin release or a positive effect on the release of some of the known acid inhibitors, or by an inhibition of gastrin binding to its receptors on the fundic cells. Our present findings (in combination with our previous findings of inhibition of pentagastrin- and bethanechol-stimulated gastric acid secretion by PYY, independent of the vagal cholinergic mechanism) indicate that the action of PYY is either direct on the parietal cells or is mediated by yet another, unidentified, inhibitor.

Are prostaglandins involved in somatostatin mediated inhibition of gastric secretion in the cat?

The role of prostaglandins in somatostatin mediated gastric inhibitory effects has been investigated in conscious cats. The effect of somatostatin on pentagastrin-, insulin- and histamine plus bethanechol-stimulated gastric acid and pepsin secretion was determined with and without indomethacin pretreatment. Somatostatin significantly inhibited acid and pepsin secretion and this effect was not diminished by cyclo-oxygenase inhibition. It is concluded that there is no evidence that endogenous prostaglandins mediate the inhibitory effects of somatostatin on gastric acid and pepsin secretion in the cat.

Somatostatin increases the ratio between gastric mucosal blood flow and gastric acid and pepsin secretion in dogs.

The effects of somatostatin on gastric mucosal blood flow (GMBF), acid secretion, and pepsin secretion were evaluated. Conscious gastric fistula dogs were used, with neutral red clearance as the method for estimating the mucosal blood flow. Somatostatin inhibited the pentagastrin- and bethanechol-stimulated gastric acid and pepsin secretion and resulted in an absolute decrease in mucosal blood flow. The ratios between GMBF and secretion (acid and pepsin) were increased during somatostatin infusion, which suggests a relative increase in mucosal blood flow and independent inhibition of gastric secretion. It may be concluded from this study that the acid- and pepsin-inhibitory effects of somatostatin are not mediated by changes in the GMBF.

Effect of serotonin on bethanechol-stimulated gastric acid secretion and gastric antral motility in dogs.

The purpose of the present study was to evaluate the effect of serotonin on bethanechol-stimulated gastric acid secretion and antral motility in conscious dogs with gastric fistula. Bethanechol stimulated the acid secretion dose-dependently and maintained the frequency and strength of the antral contractions at a high level. Serotonin inhibited the acid secretion dose-dependently, whereas the antral motility was stimulated. The acid inhibition was blocked by propranolol, and dose-response analysis showed inhibition of a non-competitive type. This study thereby shows that serotonin inhibits bethanechol-stimulated gastric acid secretion similarly to salmefamol (beta 2-adrenergic agonist)--that is, dose-dependently and non-competitively. Serotonin has been proposed to be a mediator of the beta-adrenergic influence on gastric function in vivo, but the counteracting effect of propranolol and the stimulatory effect of serotonin on motility contradict this hypothesis.

Selective inhibition of pentagastrin- and cholecystokinin-stimulated exocrine secretion by proglumide

The effectiveness and selectivity of proglumide, a putative cholecystokinin/gastrin receptor antagonist in vitro, were examined on gastric acid and pancreatic secretion in vivo. Gastric secretion was measured in conscious dogs in the basal state and during infusion of pentagastrin, histamine, or bethanechol, alone or in combination with proglumide (300 mg/kg · h). Pancreatic secretion was measured in anesthetized rats in response to cholecystokinin-octapeptide or secretin, alone or in combination with proglumide (100 mg/kg). Proglumide inhibited pentagastrin-stimulated secretion but had no effect on basal, histamine-stimulated, or bethanechol-stimulated gastric acid secretion. Inhibition of pentagastrin-stimulated secretion was of the competitive type. An apparent inhibitory constant was calculated to be 300 mg/kg · h; this dose is capable of eliciting plasma concentrations of ~1 mM. This estimate corresponds closely to that derived from measurements in isolated canine parietal cells. Proglumide also inhibited cholecystokinin-stimulated but not secretin-stimulated pancreatic secretion. The lack of effect of proglumide on basal, histamine-stimulated, or bethanechol-stimulated gastric acid secretion implies that background gastrin has no direct or synergistic influence on stimulation by other secretagogues. The selective effect of gastrin receptor antagonists contrasts with the effectiveness of muscarinic and histamine H2-receptor antagonists against secretion induced by all types of stimulants. Accordingly, the antisecretory potential of gastrin receptor antagonists is confined to digestive secretion when the effect of gastrin is optimal. Their potential as antitrophic agents in duodenal ulcer disease, however, has not been explored yet.

Prostaglandins may not mediate inhibition of gastric acid secretion by somatostatin in the rat.

The role of prostaglandins as mediators of the inhibitory effect of somatostatin on gastric acid secretion has been evaluated in conscious and anesthetized rats. The effect of somatostatin on bethanechol-stimulated gastric acid secretion was determined with or without indomethacin pretreatment. Prostaglandin synthesis inhibition (less than 90%) by indomethacin was verified with PGE2-generation assay on gastric mucosal tissue. In both conscious and anesthetized rats somatostatin significantly inhibited the stimulated acid output in the control and indomethacin pretreated groups. The present findings do not support a role for prostaglandins in the inhibition of gastric acid secretion by somatostatin in the rat.

Exogenous serotonin and gastric mucosal blood flow in conscious dogs.

The effects of serotonin on pentagastrin- and bethanechol-stimulated gastric mucosal blood flow (GMBF) and acid secretion were evaluated. Conscious gastric fistula dogs were used, with neutral red clearance as the method to estimate the mucosal blood flow. Serotonin inhibited the acid secretion, with a counteracting effect of propranolol and methysergide. Serotonin inhibited the pentagastrin- and bethanechol-stimulated GMBF after 15 min of infusion. The ratio between GMBF and acid secretion was increased during serotonin infusion, which suggests primary and independent changes in both variables. Propranolol and methysergide counteracted the serotonin inhibition of the GMBF. It may be concluded from this study that the acid-inhibitory effect of serotonin is not mediated by changes in the GMBF. The actions of serotonin on acid secretion and GMBF are mediated by specific receptors.

Effect of somatostatin on bethanechol-stimulated gastric acid secretion and gastric antral motility in dogs with gastric fistula.

The purpose of the present study was to evaluate the effect of somatostatin on gastric acid secretion and gastric antral motility in conscious dogs with gastric fistula. Infusion of bethanechol stimulated dose-dependently acid secretion, whereas the frequency and strength of antral motility was maintained at a high level. Somatostatin inhibited dose-dependently the stimulated acid secretion, whereas the effect on antral motility was more complex, acting especially on the amplitude of the contractions. The effects of somatostatin were not altered by using alpha-adrenergic, beta-adrenergic, dopaminergic, and serotonergic blocking drugs. The dose-response kinetics with four doses of bethanechol with and without somatostatin showed inhibition of a non-competitive type for gastric acid secretion and of a competitive type for antral motility with regard to amplitude.

Effect of Dopamine on Bethanechol-Stimulated Gastric Mucosal Blood Flow and Gastric Acid Secretion in Dogs with Gastric Fistula

The aim of the present study was to investigate the effect of Dopamine on bethanechol-stimulated gastric acid secretion and mucosal blood flow. dopamine was used alone and in conjunction with selective blockade of the alpha, beta, and dopaminergic receptors. An increasing and dose-dependent stimulation of gastric acid secretion was found for dopamine at 1, 5, and 10 micrograms/kg/min. A significant inhibition of gastric acid secretion was found with the highest dose of dopamine (40 micrograms/kg/min). the stimulatory effect seems to be mediated by more than one receptor, whereas the inhibition by high dopamine doses could be explained by a beta 1 stimulation. Dopamine (10 micrograms/kg/min) was found to increase the bethanechol-stimulated gastric mucosal blood flow. Phentolamine (alpha blackade) increased this dopamine-elevated blood flow further, with a significant increase in the ratio between blood flow and acid secretion, indicating a primary action of the alpha receptors on blood flow. Bethanechol stimulated the gastric acid secretion and blood flow in a parallel manner. It is concluded that alpha-receptor stimulation is the predominant directly acting factor in the regulation of gastric mucosal blood flow, whereas stimulation of beta, muscarinic, and 'gastrinergic' receptors mainly occurs indirectly via changes in parietal cell function. The main effect of dopamine seems to be on gastric motility, whereas the effect on gastric acid secretion is of minor importance.

Effect of isoprenaline on bethanechol-stimulated gastric acid secrtion and mucosal blood flow in dogs with gastric fistula.

The prupose of this study was to elucidate the effect of the beta-adrenoceptor stimulation by isoprenaline on cholinergic-stimulated gastric acid secretion and mucosal blood flow in conscious dogs with gastric fistula. Isoprenaline, a beta 1- and beta 2-agonist, was used alone and in conjunction with selective blockade of beta 2 and beta 1 receptors. A low dose of isoprenaline had no significant effect, whereas higher doses had a significant antisecretory effect. The antisecretory effect was significantly blocked by the beta 1-adrenoceptor blocker practolol but not by H 35/25, a beta 2-adrenoceptor blocker. The dose-response curve with five doses of bethanechol with and without isoprenaline was in accordance with a non-competitive inhibition. There was no significant effect on gastric mucosal blood flow, indicating that the acid inhibition was not secondary to changes in blood flow. The inhibitory effect of isoprenaline seems to be mediated by the beta 1 receptors and with an action primarily on the 'gastrinergic receptors'.

The effect of phloxin on bethanechol and histamine stimulated gastric acid secretion in rats

The effect of phloxin (Na salt of tetrabromo-tetrachlorofluorescein) on histamine- and bethanechol-stimulated gastric acid secretion was studied in anaesthetized rats. Concentrations of phloxin, equimolar with those of the stimulants, depressed the secretory response to histamine and had no influence on the bethanechol effect. The results suggest that histamine is not involved in the events triggered by bethanechol which stimulate gastric acid secretion in rats.

The effect of the histidine decarboxylase inhibitor brocresine (NSD-1055) on gastric acid secretion in rats.

Abstract The effect of the histidine decarboxylase inhibitor brocresine (NSD-1055) given by mouth, intraperitoneally or intravenously on tetragastrin-, histamine- and bethanechol-stimulated gastric acid secretion was examined in rats. Intravenous injection of brocresine slightly reduced the tetragastrin-stimulated secretion. Histamine-stimulated secretion was markedly increased by both intraperitoneal and intravenous injection of brocresine but it had no effect on the bethanechol-stimulated secretion. It was concluded that either histidine decarboxylase is not effectively inhibited by brocresine or any inhibition induced does not affect gastric acid secretion. The enhanced histamine-stimulated secretion points towards an inhibition of diamine oxidase by brocresine.

Potentiation of acid secretion in dogs

ARTICLESPotentiation of acid secretion in dogsAR CookeAR CookePublished Online:01 Apr 1969https://doi.org/10.1152/ajplegacy.1969.216.4.968MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByEffect of Isoprenaline on Bethanechol-Stimulated Gastric Acid Secretion and Mucosal Blood Flow in Dogs with Gastric Fistula19 February 2010 | Scandinavian Journal of Gastroenterology, Vol. 17, No. 5Acid Secretory Responses to Histamine, Pentagastrin, and Feeding before and after Vagal Denervation of Fundic Pouches in Cats23 February 2010 | Scandinavian Journal of Gastroenterology, Vol. 12, No. 3Potentiation by Carbachol and Aminophylline of Histamine- and db-cAMP-Induced Parietal Cell Activity in Isolated Gastric GlandsActa Physiologica Scandinavica, Vol. 99, No. 1Quantitative Histology of the Gastric Mucosa: Man, Dog, Cat, Guinea Pig, and FrogGastroenterology, Vol. 67, No. 6Duodenal Acidification: Role of First Part of Duodenum in Gastric Emptying and Secretion in DogsGastroenterology, Vol. 67, No. 1Augmentation of pentagastrin stimulated gastric secretion in the heidenhain pouch dog by amodiaquine: Inhibition of histamine methyltransferase in vivo?Agents and Actions, Vol. 3, No. 3Secretin and Cholecystokinin (CCK)Influence of cholinergic stimulation on gastric secretory response to histamine in ex vivo isolated canine stomachThe American Journal of Digestive Diseases, Vol. 17, No. 7Potentiation of Acid Output in Man by a Distention StimulusGastroenterology, Vol. 58, No. 5Gastroenterology in Australia, 1949-69.Postgraduate Medical Journal, Vol. 46, No. 534Gastric and Pancreatic Secretion in Response to Gastric Distention in DogsGastroenterology, Vol. 57, No. 3 More from this issue > Volume 216Issue 4April 1969Pages 968-973 Copyright & PermissionsCopyright © 1969 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1969.216.4.968PubMed4887279History Published online 1 April 1969 Published in print 1 April 1969 Metrics