Antisecretory effects of galanin and its putative antagonists M15, M35 and C7 in the rat stomach

The neuropeptide galanin has been reported to have a wide range of biological actions both in the central nervous system and in the gastrointestinal tract. Recent works led to the discovery of selective galanin receptor antagonists including M15 (galanin_1-12-Pro- substanceP_5-11-amide), M35 (galanin_1-12-Pro-bradykinin_2-9-amide) and C7 (galanin_1-12-Pro-spantide-amide). These antagonists were shown to competitively inhibit actions of galanin in the central nervous system. The present study was designed to investigate the effect of galanin, M15, M35 and C7 on gastric acid secretion and gastric emptying. Pentagastrin-stimulated gastric acid secretion was inhibited by galanin (0.1-9 nmol·kg^-1·h^-1, i.v.) in a dose-dependent manner (ID₅₀= 1.8 ± 0.3 nmol·kg^-1·h^-1). When 9 nmol·kg^-1·h^-1 galanin infusion was given, inhibition became almost complete. M15, M35 and C7 (1-9 nmol·kg^-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 regulation of gastric acid secretion but not in the control of gastric emptying of liquids in rats. Its antisecretory action on the stomach is mediated by galanin receptors that are distinct from those in the central nervous system. (C) 2000 Elsevier Science Ltd.