Antisecretory effects of galanin and its putative antagonists M15, M35 andC7 in the rat stomach

The neuropeptide galanin has been reported to have a wide range of biologic al actions both in the central nervous system and in the gastrointestinal t ract. Recent works led to the discovery of selective galanin receptor antag onists including M15 (galanin(1-12)-Pro-substanceP(5-11)-amide), M35 (galan in(1-12)-Pro-bradykinin(2-9)-amide) and C7 (galanin(1-12)-Pro-spantide-amid e). These antagonists were shown to competitively inhibit actions of galani n in the central nervous system. The present study was designed to investig ate the effect of galanin, M15, M35 and C7 on gastric acid secretion and ga stric emptying. Pentagastrin-stimulated gastric acid secretion was inhibite d by galanin (0.1-9 nmol.kg(-1).h(-1), i.v.) in a dose-dependent manner (ID 50 = 1.8 +/- 0.3 nmol.kg(-1)h(-1)). When 9 nmol.kg(-1)h(-1) galanin infusio n was given, inhibition became almost complete. M15, M35 and C7 (1-9 nmol.k g(-1).h(-1)) did not modify responses of the stomach to galanin, but acted as agonists of galanin on acid secretion. Neither galanin nor its putative antagonists affected the emptying of non-caloric liquids from the stomach. In conclusion, galanin may play an antisecretory role in the re,regulation of gastric acid secretion but not in the control of gastric emptying of liq uids in rats. Its antisecretory action on the stomach is mediated by galani n receptors that are distinct from those in the central nervous system. (C) 2000 Elsevier Science Ltd. Published by Editions scientifiques et medicale s Elsevier SAS.