Effects of Cholecystokinin on Adenylate Cyclase Activity in Dispersed Pancreatic Acinar Cells

Abstract

In dispersed acinar cells prepared from guinea pig pancreas secretin and vasoactive intestinal peptide (VIP) but not carboxyl terminal octapeptide of cholecystokinin (CCK-OP) or [Ala32]CCK-OP increased cyclic AMP. At concentrations above 10-5 m CCK-OP as well as the 32-alanine analogue inhibited noncompetitively the increase in cyclic AMP caused by secretin or VIP. In homogenates of acinar cells secretin, VIP and CCK-OP but not [Ala32]CCK-OP increased adenylate cyclase activity. At concentrations below 10− 5 m , [Ala32]CCK-OP potentiated the increase in adenylate cyclase caused by secretin or VIP. At concentrations above 10-5 m , CCK-OP and the 32-alanine analogue inhibited noncompetitively the increase in adenylate cyclase activity caused by secretin and VIP. Analogues and fragments of CCK-OP showed a pattern for increasing adenylate cyclase activity which differed from that for increasing calcium outflux from intact acinar cells. These findings suggest that in addition to the class of receptors which mediate the effects of CCK-OP on calcium outflux and cyclic GMP, pancreatic acinar cells possess two additional classes of receptors via which CCK-OP alters adenylate cyclase activity. One of these two classes of receptors is accessible only in broken cell preparations and when occupied by CCK-OP increases adenylate cyclase activity, whereas when occupied by the 32-alanine analogue potentiates the effects of secretin or VIP on adenylate cyclase activity. The other class of receptors is accessible to CCK-OP or [Ala32]CCK-OP in intact cells as well as in homogenates, and when occupied by either of these two peptides inhibits the stimulation of adenylate cyclase activity by secretin, VIP, or CCK-OP.