FUNCTIONAL COUPLING BETWEEN THE CYCLIC ADENOSINE-MONOPHOSPHATE PATHWAY AND CHOLECYSTOKININ SECRETION IN RIN CELLS

The cellular events associated with cAMP-dependent cholecystokinin (CC K) release were investigated with an X-ray induced rat pancreatic tumo r cell line (RIN 1056 E). Forskolin dose-dependently stimulated the re lease of CCK. Agents that increase [Ca2(+)](i) (thapsigargin, Bay K 86 44, ionomycin) also stimulated the release of CCK. Conversely, absence of extracellular Ca2+ or cell treatment with various calcium channel blockers strongly reduced the forskolin-induced CCK release. Finally, the cAMP-kinase inhibitor H89, the calmodulin antagonist W7 and the Ca /calmodulin-dependent protein-kinase II inhibitor KN62 strongly inhibi ted the forskolin-evoked CCK secretion. We conclude that the release o f CCK via a cAMP-dependent pathway is dependent on the activation of v oltage-dependent calcium channels and may implicate protein kinase A, calmodulin and the Ca/calmodulin-dependent protein kinase II. (C) 1994 Academic Press, Inc.