Examination of somatostatin involvement in the inhibitory action of GIP, GLP‐1, amylin and adrenomedullin on gastric acid release using a new SRIF antagonist analogue

Abstract
The effect of a new type 2 selective somatostatin (SRIF) receptor antagonist (DC‐41‐33) on somatostatin‐induced inhibition of pentagastrin‐stimulated gastric acid secretion in conscious, chronic gastric fistula equipped rats was studied. Infused intravenously, DC‐41‐33 dose‐dependently inhibits SRIF‐induced inhibition of pentagastrin‐stimulated gastric acid secretion with an IC50 of 31.6±1.2 nmol kg−1 versus 10 nmol kg−1 SRIF and blocks the inhibitory effects of SRIF when simultaneously co‐infused. Its effectiveness provides additional evidence that SRIF‐inhibition of gastric acid release is a SRIF type 2 receptor‐mediated process. DC‐41‐33 is able to completely reverse the inhibitory effect of glucose‐dependent insulinotropic polypeptides, GIP and GIP‐(1–30)NH2, and glucagon‐like polypeptide, GLP‐1(7‐36)NH2, on pentagastrin‐stimulated gastric acid secretion thus confirming that they exert these effects through stimulation of endogenous SRIF release. DC‐41‐33 only partially blocks potent amylin and adrenomedullin‐induced inhibition of gastric acid secretion, therefore suggesting that somatostatin may not function as a primary mediator in the action of these peptides. Our results indicate that DC‐41‐33, is a potent in vivo inhibitor of exogenous and endogenous SRIF in rats. It represents a new class of SRIF analogues which should eventually provide excellent tools for further evaluating the many physiological roles of SRIF and its five receptor subtypes. British Journal of Pharmacology (1998) 125, 1081–1087; doi:10.1038/sj.bjp.0702160