Angiotensin II Receptors and Aldosterone Production in Rat Adrenal Glomerulosa Cells

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Abstract
Specific receptors for angiotensin II (A II) were demonstrated in membrane fractions and collagenase-dispersed cells from the zona glomerulosa of the rat adrenal gland. The equilibrium association constant (Ka) of the A II binding sites was similar in particulate fractions (2.0 .+-. 0.4 (SE) .times. 109 M-1) and intact glomerulosa cells (1.8 .+-. 0.3 .times. 109 M-1). Specific binding of [125I]iodo-A II was enhanced by increasing Na concentration, and in the presence of dithiothreitol, EDTA and EGTA. Plasma membrane fractions prepared by density gradient centrifugation showed increased binding of [125I]iodo-A II, and were correspondingly enriched in adenylate cyclase and Na-K-dependent ATPase. Steroid production by collagenase-dispersed adrenal glomerulosa cells was highly responsive to A II and ACTH. Significant increases in aldosterone and corticosterone production were elicited by A II concentrations as low as 3 .times. 10-11 M, equivalent to normal blood levels of A II in rats (5 .times. 10-11 M). The maximum increase in aldosterone production, of 6-7 times the basal value, was obtained at 10-9 M A II. Dispersed capsular cells were also highly sensitive to ACTH, responding to concentrations down to 3 .times. 10-12 M with increased aldosterone production, reaching a maximum aldosterone response of 20-fold above the basal value. The magnitudes of the aldosterone and corticosterone responses to A II in capsular and fasciculata-reticularis cells were commensurate with the distribution of A II receptors, which were 11-fold more concentrated in capsular cells. The ability of A II to evoke aldosterone production at physiological concentrations, and the correspondence between A II binding and steroidogenesis in capsular cells, domonstrate the functional importance of A II receptor sites in the zona glomerulosa of the rat adrenal cortex.