Specific effects of agonists of the calcium messenger system on secretion of 'late-pathway' steroid products by intact tissue and dispersed cells of the rat adrenal zona glomerulosa.
Recent data have implicated the phosphatidylinositol/calcium second-messenger system in the control of aldosterone secretion by the adrenal zona glomerulosa. However, in the rat adrenal there are few reports of a direct effect of protein kinase C activation on steroid secretion, while the effects of calcium mobilization may be variable. Since the rat adrenal zona glomerulosa is sensitive to the mode of tissue preparation, these mechanisms were reinvestigated in intact (non-dispersed) capsular tissue and collagenase-dispersed zona glomerulosa cells. Steroidogenesis in the intact zona glomerulosa was markedly affected by agonists of the calcium messenger system. Most notably, aldosterone and 18-hydroxycorticosterone (18-OH-B) secretion were stimulated by A23187 (100 nmol to 10 mumols/l) and BAY K 8644 (500 nmol/l). Phorbol 12-myristate 13-acetate (TPA; 1 pmol to 1 mumol/l) stimulated aldosterone secretion at all doses and caused a dose-dependent increase in 18-OH-B and 18-hydroxydeoxycorticosterone (18-OH-DOC) secretion. Corticosterone secretion was slightly increased in the presence of A23187 but not by TPA or BAY K 8644. Production of 18-OH-DOC was unaffected by A23187 and BAY K 8644. The calcium channel antagonist verapamil (10 mumols/l) inhibited ACTH-stimulated aldosterone secretion by the intact zona glomerulosa but had no effect on corticosterone secretion. Verapamil (10 mumols/l) also inhibited the increase in aldosterone secretion by collagenase-dispersed zona glomerulosa cells stimulated by ACTH (100 fmol to 100 nmol/l), angiotensin II (100 pmol to 10 nmol/l) and potassium (5.9 and 8.4 mmol/l); stimulated corticosterone secretion was unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)
Vinson
G P
GP
Department of Biochemistry, St Bartholomew's Hospital Medical College, London.
Laird
S M
SM
Whitehouse
B J
BJ
Hinson
J P
JP
D015069:18-Hydroxycorticosterone / Q000378:metabolism*; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology*; D002118:Calcium / Q000037:antagonists & inhibitors* / Q000502:physiology; D002478:Cells, Cultured; D003345:Corticosterone / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D015290:Second Messenger Systems / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015384:Zona Glomerulosa / Q000166:cytology* / Q000378:metabolism / Q000502:physiology
D000001:Calcimycin; D000450:Aldosterone; D015069:18-Hydroxycorticosterone; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D003345:Corticosterone