CHIEF CELLS POSSESS SOMATOSTATIN RECEPTORS REGULATED BY SECRETAGOGUESACTING THROUGH THE CALCIUM OR CAMP PATHWAY

Inhibition both in vivo and in vitro of pepsinogen secretion by somato statin (SS) and the histological demonstration that fundic D-cells con tain long cytoplasmic processes extending to chief cells suggest a pos sible direct effect of SS on chief cell function. The aim of the prese nt study was to determine whether SS interacts directly with receptors on isolated gastric chief cells and, if so, how SS alters cell functi on. Binding of I-125-[Tyr(11)]SS14 to chief cells was saturable, time and temperature dependent, and was inhibited by both SS14 (K-i 1.6 nM) and SS28 (K-i 5.2 nM). SMS-201-995 was 1,300-fold less potent than SS 14. Calcium-mobilizing secretagogues reduced binding of I-125-[Tyr(11) ]SS14 With efficacies of cholecystokinin octapeptide (CCK-8) > carbach ol > gastrin. Adenosine 3',5'-cyclic monophosphate (cAMP)-activating s ecretagogues also inhibited binding with efficacies of secretin > vaso active intestinal polypeptide (VIP). 12-O-tetradecanoylphorbol 13-acet ate (TPA) or A-23187 also decreased binding. Analyses demonstrated tha t CCK-8 and TPA were decreasing the affinity of SS receptors for I-125 -[Tyr(11)]SS14 without affecting their binding capacity. Both SS14 and SS28 at a maximally effective concentration inhibited cAMP production caused by VIP or secretin (20-30%) but did not alter cytosolic calciu m ([Ca2+](i)), inositol phosphates, or pepsinogen release. We conclude that chief cells possess SS receptors with a high affinity for both S S14 and SS28 but low affinity for SMS-201-995 and thus resemble the SS B receptors described in the rat cerebral cortex. Although occupation of these receptors by SS has no effect on pepsinogen release induced b y secretagogues acting through either the calcium or the cAMP pathway, SS receptor occupation is regulated by agents activating phospholipas e C, adenylate cyclase, protein kinase C, and [Ca2+](i).