title: Angiotensin-II induces changes in the cytosolic sodium concentration in bovine adrenal glomerulosa cells: involvement in the activation of aldosterone biosynthesis.
abstract: The homeostasis of cytosolic free calcium ([Ca2+]i) and intracellular free sodium ([Na+]i) are linked in many cell types. We, therefore, studied the effect on [Na+]i of two physiological stimulators of aldosterone synthesis that trigger the calcium messenger system, angiotensin-II (Ang II) and potassium ion (K+), in cultured bovine adrenal glomerulosa cells, using the intracellular fluorescent probe for sodium, sodium benzofuran isophthalate. Ang II induced a concentration-dependent and sustained increase in [Na+]i, from a resting value of 9.2 +/- 3.5 to a maximum of 48.5 +/- 5.5 mM (n = 14). This [Na+]i response was mediated by receptors of the AT1 subtype, because it was abolished by losartan (DuP 753). K+ (15 mM) induced a weaker [Na+]i response, from 5.9 +/- 2.6 to 16.8 +/- 2.5 mM (n = 9). In freshly prepared cells, basal [Na+]i was significantly higher (23.9 +/- 1.8 mM; n = 14; P < 0.01) than in cultured cells. Atrial natriuretic peptide, which is known to affect sodium transport in various cell types, did not alter the [Na+]i response elicited by Ang II. Ethylisopropylamiloride, an inhibitor of Na+/H+ exchange, and dichlorobenzamyl, an inhibitor of Na+/Ca2+ exchange, both inhibited in a concentration-dependent manner the Ang II- and K(+)-induced aldosterone response. Isoosmotic replacement of extracellular Na+ markedly reduced basal aldosterone synthesis. Under these conditions, the concentration-response curve for Ang II-induced aldosterone synthesis was shifted to the right, and its maximum was strikingly diminished. These results show that Ang II and, to a lesser extent, K+ induce significant changes in [Na+]i in bovine glomerulosa cells. These [Na+]i changes probably occur through the Na+/H+ and Na+/Ca2+ exchangers and are likely to play a role in activation of the steroidogenic cascade.
authors.affiliation: Division of Endocrinology, University Hospital, Geneva, Switzerland.
authors.forename: V
authors.initials: V
authors.lastname: van der Bent
authors.forename: C
authors.initials: C
authors.lastname: Demole
authors.forename: E I
authors.initials: EI
authors.lastname: Johnson
authors.forename: M F
authors.initials: MF
authors.lastname: Rossier
authors.forename: C P
authors.initials: CP
authors.lastname: Python
authors.forename: M B
authors.initials: MB
authors.lastname: Vallotton
authors.forename: A M
authors.initials: AM
authors.lastname: Capponi
mesh_terms: D000450:Aldosterone / Q000096:biosynthesis*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D001572:Benzofurans; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D004988:Ethers, Cyclic; D005456:Fluorescent Dyes; D006706:Homeostasis; D011188:Potassium / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger; D015384:Zona Glomerulosa / Q000187:drug effects / Q000378:metabolism*
chemical_list: D001572:Benzofurans; D002352:Carrier Proteins; D004988:Ethers, Cyclic; D005456:Fluorescent Dyes; D019831:Sodium-Calcium Exchanger; D000804:Angiotensin II; C061665:sodium-binding benzofuran isophthalate; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D012964:Sodium; D011188:Potassium