REGULATION OF THE ACTION OF THE NOVEL CHOLECYSTOKININ-RELEASING PEPTIDE DIAZEPAM-BINDING INHIBITOR BY INHIBITORY HORMONES AND TAUROCHOLATE

Diazepam binding inhibitor (DBI1-86) has recently been isolated in sea rch for a cholecystokinin (CCK)-releasing peptide in the duodenum that is responsible for the feedback regulation of exocrine pancreatic sec retion. Synthetic porcine DBI1-86 stimulates CCK release in vivo and i n vitro from isolated intestinal mucosal cells. We postulated that DBI intraduodenally releases CCK in a paracrine fashion and might be the missing link in the feedback regulation of exocrine pancreatic secreti on. Somatostatin, peptide YY (PYY) and taurocholate are known to inhib it feedback-stimulated CCK release in the rat. In this study, we inves tigated the effect of somatostatin, PYY and taurocholate on DBI-stimul ated CCK secretion. Dispersed rat intestinal mucosal cells were prepar ed from the proximal small bowel and continuously perfused. The perfus ate was collected and the release of CCK into the medium was measured. DBI1-86 dose-dependently stimulated CCK release, with a maximal effec t at 10(-9) M. Somatostatin blocked the DBI-stimulated CCK release. Pr etreatment of the cells with pertussis toxin fully reversed the inhibi tory effect of somatostatin on DBI-stimulated CCK secretion, suggestin g that somatostatin exerts its action by an inhibitory G-protein. In c ontrast, PYY (10(-6) M) and taurocholate (10(-6) M) did not affect DBI stimulated CCK levels, indicating that they act through different mec hanisms to inhibit feedback-stimulated CCK release. (C) 1998 Elsevier Science B.V.