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 (CCK) in response to other physiological stimuli. 2. Fatty acids elicited a chain length- and dose-dependent stimulation of CCK secretion. Dodecanoic acid (C12) was most effective, producing up to a 5-fold increase in CCK secretion. Fatty acids with less than ten carbon atoms did not increase secretion. The chain length dependence of these effects mimics closely fatty acid-induced CCK secretion previously observed in humans in vivo. 3. Esterification of C12 abolished CCK secretion, indicating a critical role for a free carboxyl group in eliciting secretion. In contrast, modification of the methyl terminus had no effect on C12-induced secretion. The non-metabolizable 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 antagonist nicardipine. In contrast, C8 produced a smaller and more transient Ca2+ response. C12-induced CCK secretion was also blocked by nicardipine. 5. These data suggest that fatty acids can interact directly with enteroendocrine cells to stimulate CCK secretion via increases in intracellular calcium mediated primarily by L-type Ca2+ channels.
Department of Medicine, Section of Gastrointestinal Science, University of Manchester, Hope Hospital, Salford, UK.
J T
JT
McLaughlin
R B
RB
Lomax
L
L
Hall
G J
GJ
Dockray
D G
DG
Thompson
G
G
Warhurst
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002766:Cholecystokinin / Q000378:metabolism*; D003470:Culture Media; D004703:Endocrine System / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005227:Fatty Acids / Q000494:pharmacology*; D051379:Mice; D009529:Nicardipine / Q000494:pharmacology; D011863:Radioimmunoassay; D013268:Stimulation, Chemical; D013329:Structure-Activity Relationship; D013618:Tachyphylaxis / Q000502:physiology; D014407:Tumor Cells, Cultured
D002121:Calcium Channel Blockers; D003470:Culture Media; D005227:Fatty Acids; D002766:Cholecystokinin; D009529:Nicardipine; D002118:Calcium