REGULATION OF CHOLECYSTOKININ SECRETION BY CALCIUM-DEPENDENT CALMODULIN KINASE-II - DIFFERENTIAL-EFFECTS OF PHENYLALANINE AND CAMP

The release of cholecystokinin was investigated in STC-1 cells, an int estinal cholecystokinin-secreting cell line. Fifteen minute incubation of cells with the amino acid, L-phenylalanine (20 mM), or the phospho diesterase inhibitor, IBMX (100 mu M), stimulated cholecystokinin secr etion. stimulation of secretion by both agents was associated with an increase in cytosolic calcium and was inhibited by the calcium channel blocker, diltiazem (10 mu M). The calcium-calmodulin kinase II inhibi tor, KN-62 (1.4 mu M), markedly reduced IBMX-stimulated secretion, but had no effect on phenylalanine-mediated activity. KN-62 also inhibite d IBMX-induced increases in cytosolic calcium, suggesting that cAMP ma y activate diltiazem-sensitive calcium channels by a calmodulin-depend ent process. (C) 1994 Academic Press, Inc.