Stimulation by serum of aldosterone production from rat adrenal glomerulosa cells in vitro: relationships to K+, serotonin and angiotensin II

Abstract

Normal human serum markedly stimulated aldosterone production from rat adrenal glomerulosa cells incubated in Krebs Ringer bicarbonate medium (KRBGA). The effect was dose-related. In [K+] 3.6 mM KRBGA medium, serum stimulated aldosterone output to higher levels than those produced by maximal doses of serotonin (5 HT), angiotensin II (All) or high [K+] (8.4 mM). Cells maximally stimulated by high [K+], 5 HT or All in KRBGA medium were further stimulated by serum. The angiotensin analogue, [Sar1, Ala8]-AII abolished the effect of All but not that of high [K+] or serum.Basal and ACTH-stimulated corticosterone outputs of rat fasciculata cells were not significantly affected by sera known to stimulate glomerulosa cells. Aldosterone stimulating activity of serum was dialysable and fully recovered in a serum ultrafiltrate. The serotonin blockers methysergide and metergoline abolished the aldosterone stimulating activity of serum but also depressed basal aldosterone output and methysergide reduced K+-stimulated output. Chymotrypsin digestion abolished the aldosterone stimulating activity of All but not that of serotonin or serum. 5 HT concentration of sera was measured and found to be near the threshold for aldosterone stimulation. Sodium loading and depletion of 4 normal subjects did not consistently modify the aldosterone stimulating activity of their sera. In a supplemented medium (RPMI 1640), basal and K+-stimulated aldosterone outputs were higher than in KRBGA medium. Under these conditions serum stimulated aldosterone output in normal [K+] medium but only marginally in high [K+] medium. In RPMI medium, serum did not further stimulate cells maximally stimulated with serotonin.Serum appears to stimulate aldosterone production from glomerulsoa cells by two different mechanisms: One is probably due to a serotonin-like substance. A separate effect of serum, seen only in KRBGA medium, is to enhance aldosterone output of glomerulosa cells maximally stimulated by K+, 5 HT or All.