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(Hypertension. 1998;31:463.)
© 1998 American Heart Association, Inc.

Scientific Contributions

Different Signaling Pathways Mediate Stimulated Secretions Of Endogenous Ouabain and Aldosterone From Bovine Adrenocortical Cells

Jui R. Shah; James Laredo; Bruce P. Hamilton; John M. Hamlyn

From the Departments of Physiology (J.R.S., J.M.H) and Medicine (B.P.H.), University of Maryland at Baltimore; the Department of Surgery (J.L.), Beth Israel Hospital, Harvard University, Boston; and the Veterans Administration Medical Center (B.P.H.), Baltimore.

Correspondence to John M. Hamlyn, PhD, Department of Physiology, School of Medicine, University of Maryland at Baltimore, 655 West Baltimore Street, Baltimore, MD 21201. E-mail jhamlyn{at}umabnet.ab.umd.edu

Angiotensin II stimulates secretion of corticosteroids and an ouabain-like compound from adrenocortical cells. The angiotensin AT₁ and AT₂ receptor subtypes have been linked with stimulated secretion of aldosterone and endogenous ouabain, respectively, but the second messenger mechanisms involved in the latter secretion are not known. Accordingly, we investigated the effects of several pharmacological agents that affect signaling pathways on the basal and stimulated secretions of aldosterone and endogenous ouabain from primary cell cultures of bovine adrenocortical cells. The AT₂ receptor antagonist, PD 123319, blocked the effects of angiotensin II on secretion of endogenous ouabain but not aldosterone. Treatment of the cells with either dibutyryl cAMP, a membrane permeant analog, or the phorbol ester tetradecanoyl phorbol acetate stimulated aldosterone secretion but had no effect on the secretion of endogenous ouabain. On the other hand, the membrane permeant analog, 8BcGMP, maximally activated secretion of endogenous ouabain whereas incubation of cells with sodium orthovanadate blocked angiotensin II stimulated secretion of endogenous ouabain. Neither 8BcGMP nor sodium orthovanadate affected the basal or stimulated components of aldosterone secretion. These results show that the secretions of aldosterone and endogenous ouabain from bovine adrenocortical cells are mediated by different intracellular signaling mechanisms and provide evidence that the adrenal secretions of these steroids are regulated differently.

Key Words: angiotensin II receptors • sodium pump • phosphotyrosine phosphatase • signal transduction • steroids • cardiac glycosides

Abbreviations: 8BcGMP = 8-bromoguanosine 3':5'-cyclic monophosphate • ACTH = adrenocorticotropic hormone • AII = angiotensin II • AT₁ = angiotensin II type 1 • AT₂ = angiotensin II type 2 • BAC = bovine adrenocortical cells • BAG = bovine adrenal glomerulosa • DAG = diacylglycerol • dbcAMP = N⁶-2'-o-dibutyryladenosine 3':5'-cyclic monophosphate • DTFA = ditrifluoroacetate • EO = endogenous "ouabain" • IP₃ = 1,4,5-inositol trisphosphate • MAP = mitogen-activated protein • PD123319 = (s)-1-{[4-(dimethylamino)-3-methylphenyl]methyl}-5-(diphenylacetyl)-4,5,6,7-tetrahydro-1H-imidazo(4,5-c)pyridine-6-carboxylic acid • PBS = phosphate buffered saline • PKC = protein kinase C • PLC = phospholipase C • PTPase = phosphotyrosine phosphatase • RIA = radioimmunoassay • TPA = tetradecanoyl phorbol acetate • ZG = zona glomerulosa

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