Different actions of secretin and Gly-extended secretin predict secretin receptor subtypes

Only one secretin receptor has been cloned and its properties characterized in native and transfected cells. To test the hypothesis that stimulatory a nd inhibitory effects of secretin are mediated by different secretin recept or subtypes, pancreatic and gastric secretory responses to secretin and sec retin-Gly were determined in rats. Pancreatic fluid secretion was increased equipotently by secretin and secretin-Gly, but secretin was markedly more potent for inhibition of basal and gastrin-induced acid secretion. In Chine se hamster ovary cells stably transfected with the rat secretin receptor, s ecretin and secretin-Gly equipotently displaced I-125-labeled secretin (IC5 0 values 5.3 +/- 0.5 and 6.4 +/- 0.6 nM, respectively). Secretin, but not s ecretin-Gly, caused release of somatostatin from rat gastric mucosal D cell s. Thus the equipotent actions of secretin and secretin-Gly on pancreatic s ecretion appear to result from equal binding and activation of the pancreat ic secretin receptor. Conversely, secretin more potently inhibited gastric acid secretion in vivo, and only secretin released somatostatin from D cell s in vitro. These results support the existence of a secretin receptor subt ype mediating inhibition of gastric acid secretion that is distinct from th e previously characterized pancreatic secretin receptor.