Effects of angiotensin IV and angiotensin-(1-7) on basal and angiotensin II-stimulated cytosolic Ca2+ in mesangial cells.
This study analyzed the influence of two main metabolites of angiotensin II, angiotensin IV and angiotensin-(1-7), on basal and angiotensin II-dependent [Ca2+](i) in rat mesangial cells. Angiotensin IV behaved as a weak agonist. Its effects were abolished by angiotensin AT(1) receptor antagonists. Treatment with angiotensin II abolished the effect of a subsequent treatment with angiotensin IV whereas two successive angiotensin IV-dependent [Ca2+](i) peaks were obtained. Angiotensin II increased [Ca2+](i) in a Ca2+-free medium whereas angiotensin IV was inactive. Leucine-valine-valine-hemorphin 7, a hemorphin specific for the angiotensin AT(4) receptor, was devoid of any agonistic or antagonistic effect. In contrast, angiotensin-(1-7), if without influence on basal [Ca2+](i), inhibited angiotensin II- and angiotensin IV-dependent [Ca2+](i) increases. Total inhibition of the angiotensin IV effect was obtained whereas association of angiotensin-(1-7) to 8-(NN-diethylamino)-octyl-3,4,5-trimethoxybenzoate, an inhibitor of inositol phosphate-mediated Ca2+ release, was necessary to suppress the effect of angiotensin II. These results provide evidence that angiotensin II metabolites may participate in the control of [Ca2+](i) in mesangial cells at the initial stage of binding to the angiotensin AT(1) receptors.
INSERM U. 489, Hôpital Tenon, 4 rue de la Chine, 75020 Paris, France.
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Chansel
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Vandermeersch
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Oko
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Curat
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Ardaillou
D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D002118:Calcium / Q000378:metabolism*; D018929:Cell Culture Techniques; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D007295:Inositol Phosphates; D010446:Peptide Fragments; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-; D000803:Angiotensin I; C118790:angiotensin I (1-7); C081643:candesartan; D002118:Calcium