Fatty acids stereospecifically stimulate neurotensin release and increase [Ca2+]i in enteric endocrine cells.

Abstract

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.

• Authors: D L Barber, A M Cacace, D T Raucci, M B Ganz
• Journal: The American journal of physiology (Am J Physiol) Vol. 261 Issue 3 Pt 1 Pg. G497-503 (Sep 1991) ISSN: 0002-9513 [Print] United States
• PMID: 1887896 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Fatty Acids, Nonesterified
• Neurotensin
• Protein Kinase C
• Calcium

Topics

• Adrenal Gland Neoplasms
• Animals
• Calcium (metabolism)
• Cell Line
• Cells, Cultured
• Dogs
• Dose-Response Relationship, Drug
• Fatty Acids, Nonesterified (pharmacology)
• Ileum
• Intestinal Mucosa (drug effects, physiology)
• Kinetics
• Neurotensin (metabolism)
• Pheochromocytoma
• Protein Kinase C (metabolism)
• Rats
• Stereoisomerism
• Structure-Activity Relationship
• Thyroid Neoplasms