Specificity and mechanism of fatty acid inhibition of aldosterone secretion.
We have shown that unesterified, unsaturated long-chain fatty acids inhibit angiotensin II (AII) binding to receptors in adrenal glomerulosa cells. In this report, we show that oleic and arachidonic acids are specific inhibitors of the AT1 subtype of angiotensin receptor, and exert no effect on receptors of the AT2 subtype. By contrast, decanoic acid is a weak inhibitor of the AT2 subtype only. Our previous work on a post-receptor locus of inhibition by fatty acids of aldosterone biosynthesis showed that the 18-oxidase step is uniquely sensitive. In brief, the first and last steps involved in angiotensin-stimulated aldosterone secretion are particularly sensitive to inhibition by fatty acids. These results suggest a specific role for unesterified fatty acids in regulation of salt and water metabolism.
Goodfriend
T L
TL
William S. Middleton Memorial Veterans Hospital, University of Wisconsin, Madison 53705, USA.
Lee
W M
WM
Ball
D L
DL
Elliott
M E
ME
D000313:Adrenal Medulla / Q000378:metabolism; D000450:Aldosterone / Q000378:metabolism*; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D003652:Decanoic Acids / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D008041:Linoleic Acids / Q000494:pharmacology; D009829:Oleic Acids / Q000494:pharmacology; D011945:Receptors, Angiotensin / Q000378:metabolism*; D015384:Zona Glomerulosa / Q000378:metabolism
D003652:Decanoic Acids; D005231:Fatty Acids, Unsaturated; D008041:Linoleic Acids; D009829:Oleic Acids; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D000450:Aldosterone