The release ofcholecystokininwas investigated in STC-1 cells, an intestinalcholecystokinin-secreting cell line. Fifteen minute incubation of cells with the amino acid, L-phenylalanine(20 mM), or the phosphodiesterase inhibitor, IBMX (100 microM), stimulatedcholecystokininsecretion. Stimulation ofsecretionby both agents was associated with an increase in cytosolic calcium and was inhibited by the calcium channel blocker, diltiazem (10 microM). The calcium-calmodulinkinaseIIinhibitor, KN-65 (1.4 microM), markedly reduced IBMX-stimulatedsecretion, but had no effect onphenylalanine-mediated activity. KN-62 also inhibited IBMX-induced increases in cytosolic calcium, suggesting thatcAMPmay activate diltiazem-sensitive calcium channels by acalmodulin-dependent process.