Thesecretionofcholecystokininwas examined in STC-1 cells, an intestinalcholecystokinin(CCK)-secreting cell line. Exposure to the amino acid L-phenylalanineincreased release of CCK by 135%, 180%, and 251% of control levels after 15-min treatments with 5, 20, and 50 mMphenylalanine, respectively. L-Phenylalanine-inducedsecretionof CCK was inhibited by thecalciumchannel blocker diltiazem (10 microM). L-Phenylalanine(20 mM) also significantly increased cytosoliccalciumlevels in fura 2-acetoxymethyl ester (fura 2-AM)-loaded cells, and this increase was diltiazem sensitive. D-Phenylalanine, over the dose range of 5-50 mM, produced nonsignificant increases in CCK release. Treatment of STC-1 cells with 300 ng/ml of pertussis toxin for either 4 or 24 h did not significantly affect either basal release of CCK or L-phenylalanine-stimulatedsecretion. Patch-clamp recordings from cell-attached membrane patches showed a stimulation incalciumchannel activity after L-phenylalanine. These results indicate that, in STC-1 cells, L-phenylalaninestimulates release ofcholecystokininvia acalcium-dependent process.