Fatty acids stereospecifically stimulate neurotensin release and increase [Ca2+]i in enteric endocrine cells.
In primary cultures of canine enteric endocrine cells, fatty acids directly stimulated the release of neurotensin-like immunoreactivity (NTLI). This stimulatory effect was cell specific, selective for long-chain unsaturated fatty acids, and stereospecific. Saturated fatty acids of comparable chain length and trans isomers of long-chain unsaturated fatty acids had no effect on basal NTLI secretion. NTLI release in response to oleic acid (cis-11) was dose dependent with an apparent EC50 of 37 +/- 0.18 microM. Cyclooxygenase inhibitors had no effect on fatty acid-stimulated NTLI release, indicating the response was not mediated by the production of active arachidonic acid metabolites. Somatostatin (100 nM) inhibited maximal oleic acid-stimulated NTLI release by 92%. Long-chain unsaturated fatty acids also selectively and stereospecifically stimulated an increase in the mobilization of [Ca2+]i to 313.5 +/- 28.6% of resting [Ca2+]i. Staurosporine, an inhibitor of protein kinase C, dose dependently inhibited oleic acid-stimulated NTLI release with an IC50 value of 22 +/- 0.4 nM. Long-chain unsaturated fatty acids had no effect on basal NTLI secretion from rat pheochromocytoma cells and medullary thyroid carcinoma cells, two clonal lines that express NTLI. The cell-specific, selective stereospecific, and inhibitable action of fatty acids on NTLI secretion suggests that the effect of fatty acids on enteric endocrine cells is indicative of a receptor-mediated mechanism.
Barber
D L
DL
Department of Surgery, Yale University School of Medicine, New Haven 06510.
Cacace
A M
AM
Raucci
D T
DT
Ganz
M B
MB
D000310:Adrenal Gland Neoplasms; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D007082:Ileum; D007413:Intestinal Mucosa / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D009496:Neurotensin / Q000378:metabolism*; D010673:Pheochromocytoma; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013964:Thyroid Neoplasms
D005230:Fatty Acids, Nonesterified; D009496:Neurotensin; D011493:Protein Kinase C; D002118:Calcium