Effect of alpha 2-adrenoceptor agonists on gastric pepsin and acid secretion in the rat.

1. The purpose of the present study was to analyze the effects of the alpha 2-adrenoceptor agonists clonidine, guanabenz, detomidine and medetomidine on pepsin secretion in conscious rats provided with gastric chronic fistula and to compare this with acid secretion. 2. Basal interdigestive gastric secretion, which is mainly neurally driven in the rat, and the secretion directly stimulated by the two main stimulants of chief cells, cholecystokinin octapeptide (CCK8) and methacholine, were studied. 3. Basal secretion of pepsin and acid was inhibited by all four drugs with comparable EC50S. 4. CCK-stimulated pepsin and acid secretion was less sensitive than basal pepsin and acid secretion to alpha 2-adrenoceptor inhibition. 5. Methacholine-stimulated pepsin and acid secretion was not changed by clonidine and guanabenz; methacholine-stimulated acid was even marginally increased by clonidine. 6. These results do not favour the presence of alpha 2-receptors on chief cells in the rat stomach. They rather suggest that pepsin inhibition by alpha 2-adrenoceptor agonists is indirect and due to central or peripheral inhibition of the discharge of nerve fibres activating pepsin secretion.

Control of pepsin secretion by regulatory peptides in the rat stomach: comparison with acid secretion.

Previous studies of the control of pepsin secretion by neurohumoral agents showed some discrepancies between in vitro (isolated cells) and in vivo experiments. In the present work, the effects on pepsin secretion of CCK, pentagastrin, secretin, VIP, neurotensin, histamine, and methacholine were reinvestigated in conscious gastric fistula rats, in comparison to acid secretion. ED50's and doses inducing maximal responses were measured to directly compare the potency and efficacy of these substances. Methacholine was the most efficient (maximal response = 4.5 x basal level, ED50 = 1.3 mumol/kg.h) and CCK the most potent (ED50 = 1.9 nmol/kg.h) stimulant, whereas secretin was a potent (ED50 regulators of pepsin secretion in the rat. Pentagastrin and histamine did not stimulate pepsin output, as found by others with isolated chief cells in vitro. Neurotensin and large doses of VIP marginally inhibited pepsin secretion.

Antisecretory and anti-ulcer effects of morphine in rats after gastric mucosal aggression.

The effects of morphine on gastric secretion, barrier mucus and mucosal lesions were studied in pylorus-ligated rats treated with the ulcerogenic agents, indomethacin, aspirin or taurocholic acid. All three ulcerogenic agents induced significant mucosal lesions. Morphine decreased gastric acid secretion and suppressed the aspirin- and taurocholic acid-induced, but not the indomethacin-induced mucosal lesions. These results suggest that the ulcerogenic mechanisms of indomethacin and the other agents are not identical. Moreover the antiulcer effect of morphine appears to be mediated by an increased barrier mucus level: the amount of Alcian blue bound to the mucosa, an indirect estimate of the adherent mucus layer, was increased by morphine and correlated with its protective effect. All morphine effects were reversed by naloxone.

[Action of neurotensin on duodenal alkaline secretion in rats. Comparison with pancreatic and gastric secretion]. / Action de la neurotensine sur la sécrétion bicarbonatée duodénale chez le rat. Comparaison avec les sécrétions pancréatique et gastrique.

Neurotensin is released from endocrine N cells of the ileum after meals, and might take part in the regulation of bicarbonate secretion by the pancreas and duodenum. The aim of this study was to define the effect of neurotensin on duodenal bicarbonate secretion, in comparison with its effect on gastric and pancreatic secretions. Neurotensin produced a dose-related increase of duodenal bicarbonate secretion with an ED50 of 60 pmol/kg.h. The maximal effect (about 2 times the basal level) was observed with 600 pmol/kg.h. Equimolar doses (600 pmol/kg.h) of xenopsin, neuromedin N, neurotensin 8-13 produced the same effect as neurotensin 1-13. Neurotensin fragments 1-11 and 9-13 (600 pmol/kg.h) had no significant effect on duodenal bicarbonate secretion. Indomethacin, atropine, naloxone, or the CCK antagonist L364,718 had no effect on neurotensin-stimulated bicarbonate secretion. Hexamethonium and vagotomy reduced the neurotensin effect by about 50 percent (P less than 0.05). Neurotensin produced a dose-related increase of pancreatic bicarbonate secretion with an ED50 of 150 pmol/kg.h, a decrease of gastric acid secretion with an ED50 of 2,400 pmol/kg.h, and a decrease of gastric pepsin secretion with an ED50 of 2,760 pmol/kg.h. This study shows that neurotensin stimulates duodenal bicarbonate secretion in doses which may be physiological. This biological activity depends on the presence of the C-terminal 8-13 fragment. The mechanism is complex, and depends, for approximately half, on vagal fibers (sensitive or motor), nicotinic synapses, and a non cholinergic effector. The other half of the effect, still unexplained, could be a direct effect on mucosal cells. Pancreatic and duodenal bicarbonate secretions were more sensitive to neurotensin than gastric secretion (acid and pepsin).