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Molecular pharmacological approach to drug actions on the afferent and efferent fibres of the vagal nerve involved in gastric mucosal protection in rats.

Mózsik G, Dömötör A, Abdel-Salam OM

First Department of Medicine, Medical and Health Centre, University of Pécs, 7624, Pécs, Hungary, gyula.mozsik@aok.pte.hu.

BACKGROUND: Gastric mucosal protection is associated with the actions of anti-ulcer drugs or agents affecting on the afferent and/or efferent nerve fibres of the vagal nerve. AIMS: 1. To identify the dose-response curves of drugs (compounds) on the afferent vanilloid-receptor (capsaicin or resiniferatoxin-sensitive) and on efferent secretion (atropine, pirenzepine, cimetidine, ranitidine, famotidine, omeprazole, esomeprazole) basal gastric acid and stimulated gastric secretion in relation to the chemically-induced gastric mucosal damage in rats; 2. To determine the ED(50) (pD(2)) and pA(2) on the calculation of affinity and intrinsic affinity curves for these agonists/antagonists, as an indication of relative potency of effects. MATERIALS AND METHODS: The observations were carried out in rats (30 different models). RESULTS: The ED(50) values for affinities of capsaicin, resiniferatoxin were obtained in nmol/kg b.w. range, whereas the values were in the nmol/kg to mumol/kg b.w. ranges for effects on the gastric basal, stimulated (bethanechol, pentagastrin, histamine) gastric secretion, and the gastric mucosal damage-produced by different ulcerogenic agents (ethanol, HCl, aspirin, indomethacin). CONCLUSION: From the observations, that agents acting on vanilloid (capsaicin) receptors were the most potent inhibitors of acid secretion and gastric lesions from necrotizing agents, suggests that the capsaicin sensitive afferent nerves have a primary place in the efferent regulated events leading to initiation of gastric mucosal damage.

Published 22 December 2006 in Inflammopharmacology, 14(5): 243-9.
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