PEPTIDERGIC AND CHOLINERGIC NEURONS AND MEDIATORS IN PEPTONE-INDUCED GASTROPROTECTION - ROLE OF CYCLOOXYGENASE-2

This study investigates the neural pathways, mediators, and cyclooxyge nase isoenzymes involved in the gastroprotection conferred by peptone in rats. Intragastric perfusion with 8% peptone protected against gros s and histological damage induced by subsequent perfusion with 50% eth anol. The gastroprotective effect of peptone was near maximally inhibi ted by gastrin immunoneutralization, inactivation of capsaicin-sensiti ve afferent neurons, calcitonin gene-related peptide (CGRP) immunoneut ralization, blockade of gastrin receptors, CGRP, bombesin/gastrin-rele asing peptide (GRP), or somatostatin receptors, and by the nitric oxid e (NO) synthase inhibitor NG-nitro-L-arginine methyl ester and was par tially (46%) counteracted by atropine. Indomethacin and the selective cyclooxygenase-2 inhibitors NS-398 and L-745,337 dose dependently (50% inhibitory dose, 4.2, 0.8, and 1.5 mg/kg, respectively) attenuated th e peptone-induced protection. Dexamethasone was ineffective. These res ults indicate that protective effects of peptone involve endogenous ga strin and possibly somatostatin and are mediated by capsaicin-sensitiv e afferent, cholinergic, and bombesin/GRP neurons. CGRP, NO, and prost aglandins participate as essen tial mediators. The study provides evid ence that prostaglandins derived from a constitutive cyclooxygenase-2 contribute to mucosal defense in the presence of ulcerogens and thus p articipate in homeostatic functions of the stomach.