This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Polidori, C. Articles by Morini, G. Search for Related Content PubMed PubMed Citation Articles by Polidori, C. Articles by Morini, G.

Peripheral Mechanisms Involved in Gastric Mucosal Protection by Intracerebroventricular and Intraperitoneal Nociceptin in Rats

Department of Experimental Medicine and Public Health (C.P., M.M.), University of Camerino, 62032 Camerino; Department of Pharmaceutical Sciences (R.G.), University of Ferrara, 44100 Ferrara; and Department of Human Anatomy, Pharmacology, and Forensic Medicine (D.G., D.L., G.M.), University of Parma, 43100 Parma, Italy

Address all correspondence and requests for reprints to: Giuseppina Morini, Department of Human Anatomy, Pharmacology and Forensic Medicine, University of Parma, Via Volturno 39, 43100 Parma, Italy. E-mail: giuseppina.morini{at}unipr.it.

Nociceptin (N/OFQ) exerts multiple effects in the gastrointestinal tract after 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 µg/rat) or ip (10 µg/kg), significantly reduced macroscopic and histological 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, CGRP_8–37, and by the nitric oxide synthase inhibitor, N^G-nitro-L-arginine methyl ester. 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, whereas vagal nonmuscarinic pathways mediate the peripheral activity of the peptide. The neuronal circuit involving extrinsic sensory neurons, calcitonin gene-related peptide, 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.