title: Effect of ANP on sustained aldosterone secretion stimulated by angiotensin II.
abstract: The sustained aldosterone secretory response to angiotensin II (ANG II) depends on receptor-mediated increases in membrane diglyceride (DG) and an increase in calcium influx rate. These signals serve to activate membrane-associated protein kinase C (PKC) and result in enhanced phosphorylation of a unique set of proteins. These events can be mimicked by the addition of a phorbol ester, 12-O-tetra decanoyl phorbol 13-acetate (TPA), and a calcium ionophore, A23187, that bypass the initial receptor-associated events. We studied the inhibitory action of atrial natriuretic peptide (4-28 hANP) on the sustained secretory response to ANG II in isolated bovine adrenal glomerulosa cells. Although 10 nM ANP inhibited aldosterone secretion, it did not significantly alter the ANG II-elicited rise in 45Ca2+ influx rate [control (CON): 0.44 +/- 0.06; ANG II: 1.11 +/- 0.12 (P less than 0.001); ANG II + ANP: 1.18 +/- 0.14], the steady-state level of aequorin luminescence [intracellular [Ca2+] ([Ca2+]i)], or the rise in cellular DG content [CON: 0.132 +/- 0.01; ANG II: 0.194 +/- 0.01 (P less than 0.005); ANG II + ANP: 0.202 +/- 0.01 nmol/10(6) cells]. IN addition, ANP was able to inhibit aldosterone secretion stimulated by the combined addition of A23187 + TPA. When protein phosphorylation in the ANP-inhibited cells was evaluated, ANG II-induced protein phosphorylation events were preserved. In contrast to the effect of ANP, the calcium channel blocker nitrendipine abolished the ANG II-induced rise in 45Ca2+ influx rate, reduced the steady-state level of [Ca2+]i, and returned the phosphoproteins to their control states.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
authors.forename: C M
authors.initials: CM
authors.lastname: Isales
authors.forename: W B
authors.initials: WB
authors.lastname: Bollag
authors.forename: L C
authors.initials: LC
authors.lastname: Kiernan
authors.forename: P Q
authors.initials: PQ
authors.lastname: Barrett
mesh_terms: D000331:Aequorin; D000450:Aldosterone / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D008163:Luminescent Measurements; D010446:Peptide Fragments / Q000494:pharmacology*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D015290:Second Messenger Systems; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015384:Zona Glomerulosa / Q000187:drug effects / Q000378:metabolism*
chemical_list: D004075:Diglycerides; D010446:Peptide Fragments; D010750:Phosphoproteins; C081681:atrial natriuretic factor (4-28); D000804:Angiotensin II; D000001:Calcimycin; D000450:Aldosterone; D000331:Aequorin; D009320:Atrial Natriuretic Factor; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium