title: Diacylglycerol provides arachidonic acid for lipoxygenase products that mediate angiotensin II-induced aldosterone synthesis.
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.
authors.affiliation: Section of Endocrinology, USC Medical Center, Los Angeles 90033.
authors.forename: R
authors.initials: R
authors.lastname: Natarajan
authors.forename: N
authors.initials: N
authors.lastname: Stern
authors.forename: J
authors.initials: J
authors.lastname: Nadler
mesh_terms: D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000450:Aldosterone / Q000096:biosynthesis*; D000804:Angiotensin II / Q000494:pharmacology*; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism*; D001091:Arachidonate Lipoxygenases / Q000378:metabolism*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D003512:Cyclohexanones / Q000494:pharmacology; D004075:Diglycerides / Q000378:metabolism* / Q000494:pharmacology; D005989:Glycerides / Q000378:metabolism*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D008049:Lipase / Q000037:antagonists & inhibitors; D011188:Potassium / Q000494:pharmacology; D015290:Second Messenger Systems; D015384:Zona Glomerulosa / Q000187:drug effects / Q000378:metabolism*
chemical_list: D001095:Arachidonic Acids; D003512:Cyclohexanones; D004075:Diglycerides; D005989:Glycerides; D006893:Hydroxyeicosatetraenoic Acids; D000804:Angiotensin II; D016718:Arachidonic Acid; D000450:Aldosterone; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C036535:1,6-bis(cyclohexyloximinocarbonyl)hexane; D000324:Adrenocorticotropic Hormone; D001091:Arachidonate Lipoxygenases; D001092:Arachidonate 12-Lipoxygenase; D008049:Lipase; D011188:Potassium