Fatty acids stimulate cholecystokinin secretion via an acyl chain length-specific, Ca2+-dependent mechanism in the enteroendocrine cell line STC-1

1.The present study has investigated whether fatty acids directly influence peptide release from enteroendocrine cells using STC-1, a mouse intestinal endocrine tumour cell line, previously shown to release cholecystokinin (C CK) in response to other physiological stimuli. 2. Fatty acids elicited a chain length- and dose-dependent stimulation of C CK secretion. Dodecanoic acid (C12) was most effective, producing up to a 5 -fold increase in CCK secretion. Fatty acids with less than ten carbon atom s did not increase secretion. The chain length dependence of these effects mimics closely fatty acid-induced CCK secretion previously observed in huma ns in vivo. 3. Esterification of C12 abolished CCK secretion, indicating a critical rol e for a free carboxyl group in eliciting secretion. In contrast, modificati on of the methyl terminus had no effect on GIB-induced secretion. The non-m etabolizable C12 analogue 2-bromododecanoic acid was equally effective. 4. C12 elicited a marked increase in intracellular calcium levels (200-300 nM) in STC-1 cells which was abolished by the L-type Ca2+ channel antagonis t nicardipine. In contrast, C8 produced a smaller and more transient Ca2+ r esponse. C12-induced CCK secretion was also blocked by nicardipine. 5. These data suggest that fatty acids can interact directly with enteroend ocrine cells to stimulate CCK secretion via increases in intracellular calc ium mediated primarily by L-type Ca2+ channels.