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1 The e ect 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 ®stula equipped rats was studied. 2 Infused intravenously, DC-41-33 dose-dependently inhibits SRIF-induced inhibition of pentagastrinstimulated gastric acid secretion with an IC 50 of 31.6+1.2 nmol kg 71 versus 10 nmol kg 71 SRIF and blocks the inhibitory e ects of SRIF when simultaneously co-infused. Its e ectiveness provides additional evidence that SRIF-inhibition of gastric acid release is a SRIF type 2 receptor-mediated process. 3 DC-41-33 is able to completely reverse the inhibitory e ect of glucose-dependent insulinotropic polypeptides, GIP and GIP-(1 ± 30)NH 2 , and glucagon-like polypeptide, GLP-1(7-36)NH 2 , on pentagastrin-stimulated gastric acid secretion thus con®rming that they exert these e ects through stimulation of endogenous SRIF release. 4 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. 5 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 ®ve receptor subtypes.

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