Implication of phospholipase C in the steroidogenic action of angiotensin II.
Angiotensin II (AII) is a major regulator of aldosterone synthesis and secretion by the adrenal zona glomerulosa. Although it has been suggested by many authors that AII acts by increasing the turnover of inositol-lipids, these studies were mainly focussed on the identity and on the kinetics of appearance of inositol phosphates. The purpose of the present study was to establish a relationship between phospholipase C activation and steroidogenesis in the adrenal cortex. A primary culture of bovine adrenal glomerulosa cells was used. Dose-response curves for receptor occupation, inositol phosphate production and aldosterone secretion were made under the same experimental conditions, on the third day of culture. 125I-[Sar1, Val5, D-Phe8]AII binding to glomerulosa cells was progressively inhibited by increasing concentrations of AII up to 30 nM. Scatchard analyses showed a Kd of 1.9 +/- 1.1 nM and a maximal binding capacity of 49,000 +/- 4,500 receptors/cell (six experiments). Dose-response curves for AII-induced inositol 1,4,5-trisphosphate production showed an EC50 of 0.5 +/- 0.1 nM (five experiments). The threshold dose for AII-induced inositol phosphates was around 0.1 nM and the maximal effect was obtained with 30 nM AII. The AII-stimulated steroidogenesis occurred at a threshold dose around 0.03 nM and the maximal effect was obtained with 10 nM AII with an EC50 of 0.5 +/- 0.1 nM (five experiments). These results support previous suggestions that phospholipase C is involved in the steroidogenic action of angiotensin II.
Boulay
G
G
Department of Pharmacology, Faculty of Medicine, University of Sherbrooke, Quebec, Canada.
Gallo-Payet
N
N
Guillemette
G
G
D000450:Aldosterone / Q000096:biosynthesis; D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D010716:Phosphatidylinositols / Q000378:metabolism; D013256:Steroids / Q000096:biosynthesis*; D010738:Type C Phospholipases / Q000378:metabolism*; D015384:Zona Glomerulosa / Q000378:metabolism
D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D013256:Steroids; D000804:Angiotensin II; D000450:Aldosterone; D010738:Type C Phospholipases