Diacylglycerol provides arachidonic acid for lipoxygenase products that mediate angiotensin II-induced aldosterone synthesis

Rama Natarajan*, Naftali Stern, Jerry Nadler

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

The lipoxygenase products of arachidonic acid metabolism have been shown to be important mediators of stimulus secretion coupling in various endocrine tissues. We have recently shown that the 12-lipoxygenase product, 12-hydroxyeicosatetraenoic acid plays a key role as a new specific mediator of angiotensin II-induced aldosterone secretion in the adrenal. In view of the several pathways by which cellular arachidonate can be generated and the important role of diacylglycerol in angiotensin II-responses, we studied the role of diacylglycerol as the source of arachidonic acid for 12-hydroxyeicosatetraenoic formation. Treatment of normal human adrenal glomerulosa cells with the selective diacylglycerol-lipase inhibitor, RHC 80267, resulted in a dose-dependent inhibition of angiotensin II-induced aldosterone as well as 12-hydroxyeicosatetraenoic formation. These results suggest that AA derived from diacylglycerol is the precursor of 12-hydroxyeicosatetraenoic involved in angiotensin II-induced aldosterone secretion. These results reveal a new second messenger role for diacylglycerol in addition to activation of protein kinase C.

Original languageEnglish
Pages (from-to)717-724
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume156
Issue number2
DOIs
StatePublished - 31 Oct 1988
Externally publishedYes

Funding

FundersFunder number
NIH Heart Lung and Blood Institute
National Institutes of Health
National Heart, Lung, and Blood InstituteK08HL001496
National Institute of Diabetes and Digestive and Kidney DiseasesR01DK039721
American Heart Association841-GI

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