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Am J Physiol Gastrointest Liver Physiol 280: G88-G94, 2001;
0193-1857/01 $5.00
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Vol. 280, Issue 1, G88-G94, January 2001

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

Travis E. Solomon1,2, Gabor Varga3, Ning Zeng1,2, S. Vincent Wu1,2, John H. Walshdagger,1,2, and Joseph R. Reeve Jr.1,2

1 CURE: Digestive Diseases Research Center, Department of Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles 90073; 2 Digestive Diseases Division, UCLA School of Medicine, Los Angeles, California 90024; and 3 Institute of Experimental Medicine, Hungarian Academy of Sciences, H-1450 Budapest, Hungary

Only one secretin receptor has been cloned and its properties characterized in native and transfected cells. To test the hypothesis that stimulatory and inhibitory effects of secretin are mediated by different secretin receptor subtypes, pancreatic and gastric secretory responses to secretin and secretin-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 Chinese hamster ovary cells stably transfected with the rat secretin receptor, secretin and secretin-Gly equipotently displaced 125I-labeled secretin (IC50 values 5.3 ± 0.5 and 6.4 ± 0.6 nM, respectively). Secretin, but not secretin-Gly, caused release of somatostatin from rat gastric mucosal D cells. Thus the equipotent actions of secretin and secretin-Gly on pancreatic secretion appear to result from equal binding and activation of the pancreatic secretin receptor. Conversely, secretin more potently inhibited gastric acid secretion in vivo, and only secretin released somatostatin from D cells in vitro. These results support the existence of a secretin receptor subtype mediating inhibition of gastric acid secretion that is distinct from the previously characterized pancreatic secretin receptor.

posttranslational processing; receptor specificity; D cells; somatostatin

dagger Deceased 14 June 2000.




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