TY - JOUR
T1 - Diacylglycerol provides arachidonic acid for lipoxygenase products that mediate angiotensin II-induced aldosterone synthesis
AU - Natarajan, Rama
AU - Stern, Naftali
AU - Nadler, Jerry
N1 - Funding Information:
ACKNOWLEDGEMENTS This work was supported by Grant #ROIDK39721 from the NIH and American Heart Association, Los Angeles Affiliate (841-GI). Dr. Nadler is supported by NIH Heart Lung and Blood Institute "Clinical Investigator Award" #HLO1496. We thank Mirta Galmarini from Nichols Institute (San Juan Capistrano, CA) for performing some of the aldosterone assays and Wilson Dunn for his technical support. We also thank Ms. Jenny Yang for typing the manuscript.
PY - 1988/10/31
Y1 - 1988/10/31
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0023724878&partnerID=8YFLogxK
U2 - 10.1016/S0006-291X(88)80902-1
DO - 10.1016/S0006-291X(88)80902-1
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AN - SCOPUS:0023724878
SN - 0006-291X
VL - 156
SP - 717
EP - 724
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -