Central and peripheral vagal mechanisms involved in gastric protection against ethanol injury

Activation of medullary thyrotropin-releasing hormone (TRH), at a dose subt hreshold to increase gastric acid secretion, protects the gastric mucosa ag ainst ethanol injury through vagal cholinergic pathways in urethane-anaesth etized rats. Peripheral mediators involve the efferent function of capsaici n-sensitive splanchnic afferents leading to calcitonin gene-related peptide (CGRP)- and nitric oxide (NO)-dependent gastric vasodilatory mechanisms. I n addition, gastric prostaglandins participate in gastric protection throug h mechanisms independent of the stimulation of gastric mucosal blood flow a nd mucus secretion. Medullary TRH has physiological relevance in the vagal- dependent adaptive gastric protection induced by mild (acid or ethanol), fo llowed by strong, irritants. Additional neuropeptides, namely peptide YY (P YY), somatostatin analogues, CGRP and adrenomedullin, also act in the brain stem to induce a vagal-dependent gastric protection against ethanol through interactions with their specific receptors in the medulla. Central PYY and adrenomedullin act through vagal cholinergic prostaglandins and NO pathway s, while somatostatin analogue acts through vagal non-adrenergic, noncholin ergic vasoactive intestinal peptide and NO mechanisms. Although their biolo gical relevance is still to be established, these peptides provide addition al tools to investigate the multiple vagal-dependent mechanisms which incre ase the resistance of the gastric mucosa to injury.