CHOLECYSTOKININ-OCTAPEPTIDE INHIBITS CA2-DEPENDENT AMYLASE SECRETION FROM PERMEABILIZED PANCREATIC ACINI BY BLOCKING THE MGATP-DEPENDENT PRIMING OF EXOCYTOSIS()

At present little is known about how the low-affinity cholecystokinin receptor inhibits secretagogue-stimulated amylase secretion from pancr eatic acinar cells. To examine this question we have determined how ch olecystokinin octapeptide (CCK8) influences Ca2+-dependent amylase sec retion from alpha-toxin-permeabilized pancreatic acini. CCK8 significa ntly inhibited Ca2+ stimulated amylase secretion. The inhibitory actio ns of CCK8 were completely blocked by the addition of JMV-180, a speci fic antagonist for the low-affinity CCK8 receptor. Previous studies ha ve shown that Ca2+-dependent amylase secretion from alpha-toxin-permea bilized acini has two distinct phases [Padfield and Panesar (1997) Am. J. Physiol. 36, G655-660]. There is an initial rapid phase of secreti on which represents release from exocytotic sites primed by MgATP prio r to permeabilization. This is followed by a slower sustained phase of secretion which, in part, reflects the MgATP-dependent repriming of t he exocytotic machinery. CCK8 did not influence the initial rapid phas e of the Ca2+-dependent secretory response: but inhibited the second s lower sustained phase. Moreover, CCK8 was shown to inhibit the MgATP-d ependent priming of exocytosis in the acini. These results indicate th at the low-affinity CCK receptor blocks stimulated amylase secretion b y inhibiting the MgATP-dependent repriming of exocytosis.