Effect of Parietal Cell Vagotomy and Cholinergic Blockade on Gastrin Release in Man Induced by Gastrin-Releasing Peptide

Abstract

The influence of cholinergic blockade as well as vagal denervation of the oxyntic gland mucosa on the gastrin response to gastrin-releasing peptide (GRP) have been studied in patients with duodenal ulcer disease. The gastric luminal content was neutralized during the experiments. GRP induced a substantial increase in gastrin levels with a peak response already after 15 min of infusion. Vagal denervation of the parietal cell area induced a significant increase in basal gastrin concentrations and a significant enhancement of the GRP response. Two different doses of benzilonium bromide were studied and neither influenced the basal concentrations of gastrin. A significantly increased gastrin response to GRP was, however, observed after administration of both a high and a very low dose of the anticholinergic drug. Our results delineate a vagal, noncholinergic inhibitory influence on the basal gastrin release. In addition a vagally dependent oxyntopyloric mechanism inhibits the gastrin release stimulated by GRP. This inhibitory mechanism may hypothetically be a cholinergic reflex mechanism.

Regulation of gastric function by endogenous gastrin releasing peptide in humans: studies with a specific gastrin releasing peptide receptor antagonist

“…Several studies have shown that intravenous GRP/bombesin stimulate gastrin release and acid output in humans 46 7 20 This effect however may be more of a pharmacological than physiological event. The dose dependent inhibition of GRP induced acid secretion in our study demonstrates the antagonistic activity of BIM26226 in humans which has previously been shown only in animals 9…”

Defective Inhibition of Gastrin Release by Antral Distension in Duodenal Ulcer Patients

“…However, a number of observations suggest that the facilitated gastrin response in duodenal ulcer patients may partly be caused by a defective acid inhibition [ 17] in addition to other concomitantly operating mecha nisms. An anticholinergic drug irrespective of dose enhances the GRP-induced gastrin re sponse in duodenal ulcer patients [9], an ef fect that could not be reproduced in healthy volunteers. Future studies have to determine in more detail whether the gastrin cells of pep tic ulcer patients are more sensitive to cholin ergic blockade than those of healthy subjects.…”

“…The gastrin-releasing property of GRP has been suggested to be mediated via a direct effect of GRP on the antral gastrin cells [11]. However, we have recently observed that in the human antral mucosa, few GRP containing nerve fibres were seen in the gastrin cell region, pointing towards mechanisms of GRP-induced gastrin release alternative to a direct GRP innervation of gastrin cells [12], As is the case with food-induced gastrin release, cholinergic blockade also facilitates the gas trin releasing property of GRP in duodenal ulcer patients, an effect exerted also by dener vation of the oxyntic cell area of the stomach [9], These observations altogether would sug gest that the mechanisms regulating the re lease of antral gastrin are more complex than previously suggested, involving both inhibi tory and stimulatory mechanisms of which some may be conveyed via vagal fibres. The lack of intimate spatial interrelationship be tween GRP containing nerve fibres and gas trin cells may also suggest an indirect mode of action of GRP with involvement of interneu rons.…”

“…N.J.). The details regarding the accu racy and precision of the assay have previously been reported [9], For calculation of cumulative serum gas trin response to GRP we added gastrin concentrations during the hour of GRP infusion subtracted for the mean of the preinfusion values.…”