Peripheral mechanisms involved in gastric mucosal protection by intracerebroventricular and intraperitoneal nociceptin in rats

Abstract

Nociceptin (N/OFQ) exerts multiple effects in the gastrointestinal tract following central or peripheral administration. In the present study we examined the possible peripheral mechanisms mediating gastric protection by N/OFQ in rats. Gastric mucosal lesions were induced by 50% ethanol (1 ml/rat intragastrically). N/OFQ, administered either intracerebroventricularly (3 μ g/rat) or intraperitoneally (10 μ g/kg), significantly reduced macroscopic and histologic damage. The protective effect of intracerebroventricular N/OFQ was blocked by atropine, subdiaphragmatic vagotomy and bretylium. The effect of both central and peripheral N/OFQ was blocked by functional ablation of afferent nerves produced by capsaicin, by the antagonist of calcitonin gene-related peptide, CGRP8-37, and by the nitric oxide synthase inhibitor, L-NAME. These results indicate that N/OFQ increases gastric mucosal resistance to ethanol by operating both in the central nervous system and in the periphery. Vagal cholinergic and sympathetic pathways mediate the central activity of N/OFQ, while vagal non muscarinic pathways mediate the peripheral activity of the peptide. The neuronal circuit involving extrinsic sensory neurons, CGRP and nitric oxide is activated by central as well as peripheral N/OFQ. The study provides evidence that N/OFQ contributes to neurally mediated gastric mucosal protection. Copyright © 2005 by The Endocrine Society.