CENTRAL NEURAL CONTROL OF GASTRIC MUCOSAL DEFENSE

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These studies are designed to evaluate the role of the central nervous system in gastric mucosal defensive functions, with respect to neuropeptides and prostaglandins. It is hypothesized that 1) intracerebroventricular (ICV) administration of peptide or prostaglandins which reduce experimental ulceration, do so by enhancing certain aspects of mucosal defense, inhibition of acid secretion, stimulation of bicarbonate and mocus of secretion and maintenance of morosal blood flow. These effects may be mediated by change in gastic monosal prosteplandin activity; 2) that ICV administration of peptides which potentiate experimental ulceration do so by reducing mocosal defense, stimlation of gastric acid secretion, inhibition of gastric bicrbonate and mucus production and reduction in morosal blood flow. Protective compounds given ICV include neurotensin, bombesin, opioids, calcitonin, calcitonin gene related peptide, and prostaglandins E2, T2, and F2. Compounds which potentiate injury, given ICV, include thyrotropin relleasing hormone and vasoactive intestinal polypeptide. Compounds will be given ICV to rats prior to placing them in cold restraint stress or administration of 50% ethanol, acidified aspirin (20 mM) or acidified taurocholate (10mM) orally. The effect of each ICV administered compound will also be studied for its effect on mucosal blood flow measured by hydrogen gas clearance, bicarbonate secretion using a gasometer of pH-stat technique, mucus production measuring the thickness of gel mucus optically and soluble mucus as glucosamine output, and acid secretion by gravity drainage in chronic dogs prepared with a gastric fistula. In addition, the effect of these ICV administered compounds on gastric mucosal prostaglandin activity will be studied using the prostaglandin-generation technique and RIA. These observations should indicate in which instance ICV administered peptides modulate gastric mucosal defensive functions through an endogenous prostaglandin-mediated mechanism. Dose response relationships will be demonstrated. Verification of the central effect will require that peripheral administration of these compounds do not cause similar effects on gastric mucosal functions.