Functional coupling between the cyclic adenosine monophosphate pathway and cholecystokinin secretion in RIN cells.
The cellular events associated with cAMP-dependent cholecystokinin (CCK) release were investigated with an X-ray induced rat pancreatic tumor cell line (RIN 1056 E). Forskolin dose-dependently stimulated the release of CCK. Agents that increase [Ca2+]i (thapsigargin, Bay K 8644, 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 inhibited the forskolin-evoked CCK secretion. We conclude that the release of CCK via a cAMP-dependent pathway is dependent on the activation of voltage-dependent calcium channels and may implicate protein kinase A, calmodulin and the Ca/calmodulin-dependent protein kinase II.
Aucouturier
S
S
INSERM Unité 45, Hôpital Ed. Herriot, Lyon, France.
Bernard
C
C
Roche
C
C
Philippe
J
J
Chayvialle
J A
JA
Cuber
J C
JC
D007516:Adenoma, Islet Cell / Q000503:physiopathology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002766:Cholecystokinin / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D066298:In Vitro Techniques; D047428:Protein Kinase Inhibitors; D051381:Rats; D014407:Tumor Cells, Cultured
D047428:Protein Kinase Inhibitors; D005576:Colforsin; D002766:Cholecystokinin; D000242:Cyclic AMP; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium