title: Direct beta-adrenergic stimulation of aldosterone secretion in cultured bovine adrenal subcapsular cells.
abstract: Primary culture of bovine adrenal subcapsular cells was used to investigate direct effects of catecholamines on aldosterone secretion. Cells dispersed with collagenase and DNAse and cultured at high density (1.5-2 million/ml) for 3 days displayed high sensitivity to angiotensin II and ACTH, with an ED50 of 1.4 and 1.5 nM, respectively. Adrenergic agonists elicited a 4- to 6-fold stimulation of aldosterone secretion with potency order (-)isoproterenol greater than (-)epinephrine equals (-)norepinephrine greater than (+)isoproterenol, and corresponding ED50 5, 240, 213, and 3000 nM, respectively. No reproducible inhibition by dopamine of basal or stimulated levels of aldosterone secretion could be detected, but a weak stimulatory effect was sometimes observed at high concentration greater than 10 microM. (-)Isoproterenol stimulation of aldosterone production was potently inhibited by the beta-adrenergic antagonists (-)alprenolol and (+)alprenolol with potencies of 1.8 and 110 nM, respectively. The alpha-adrenergic antagonists prazosin, yohimbine, and phentolamine only weakly inhibited (-)isoproterenol stimulation with potencies of 5, 13, and 140 microM, respectively. The potent beta 2-adrenergic antagonist ICI 118.551 and the weaker beta 1-adrenergic antagonist atenolol were roughly equipotent with potencies of 0.27 and 0.44 microM, respectively. Addition of the phosphodiesterase inhibitor Ro 20-1724 at 10 microM doubled the maximum stimulation effect of (-)isoproterenol without changing the potency of the catecholamine or the basal level of aldosterone secretion, suggesting a potential role of cAMP as a mediator of isoproterenol stimulation. These results indicate the presence of a beta 1-adrenergic receptor stimulating aldosterone secretion in bovine zona glomerulosa cells. The physiological significance of direct beta-adrenergic stimulation of aldosterone production is currently being assessed.
mesh_terms: D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D000311:Adrenal Glands / Q000166:cytology / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000450:Aldosterone / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D006854:Hydrocortisone / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology; D013268:Stimulation, Chemical
chemical_list: D000318:Adrenergic beta-Agonists; D011412:Propanolamines; D011458:Prostaglandins E; D000804:Angiotensin II; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; C026777:ICI 118551; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D007545:Isoproterenol; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine