title: ANG II receptor expression and function during phenotypic modulation of rat aortic smooth muscle cells.
abstract: Angiotensin II (ANG II) receptors were investigated in primary cultured rat aortic smooth muscle cells (SMC) that expressed either a proliferative phenotype (during the growth phase) or a contractile phenotype (at postconfluence). For each phenotype, alpha-smooth muscle actin expression, 125I-labeled ANG II specific binding, D-myo-inositol 1,4,5-triphosphate [Ins(1,4,5)P3] production, and ANG II-mediated increases in intracellular calcium (Cai2+) were studied. In both phenotypes, 1) ANG II-specific high-affinity binding (KD 0.5 +/- 0.1 nM and Bmax 196 +/- 106 pmol/mg protein in proliferative state, KD 1.5 +/- 0.3 nM and Bmax 560 +/- 299 pmol/mg protein in postconfluent state) was entirely inhibited by the selective AT1-antagonist losartan as well as by [Sar1,Ala8]ANG II and ANG III; 2) the AT2-antagonist CGP 42112A was ineffective, except at very high concentrations (> or = 10 microM); 3) the specific binding of ANG II was inhibited by guanosine 5'-[gamma-thio]triphosphate; and 4) ANG II induced a losartan-sensitive increase in Ins(1,4,5)P3. In postconfluent cultures, ANG II elicited a rapid biphasic elevation in Cai2+, which was abolished by losartan, whereas in growing cultures, this response was either absent or greatly attenuated. It is concluded that AT1-receptors coupled to phospholipase C via a G protein are expressed in the proliferative as well as in the contractile SMC phenotype and that their coupling to Cai2+ release is impaired in the proliferative phenotype. No evidence for AT2-receptor expression during phenotypic modulation of SMC was found.
authors.affiliation: Université Louis Pasteur de Strasbourg, Laboratoire de Pharmacologie Cellulaire et Moléculaire, Illkirch, France.
authors.forename: C
authors.initials: C
authors.lastname: Corriu
authors.forename: P
authors.initials: P
authors.lastname: André
authors.forename: C
authors.initials: C
authors.lastname: Schott
authors.forename: M
authors.initials: M
authors.lastname: Michel
authors.forename: J C
authors.initials: JC
authors.lastname: Stoclet
mesh_terms: D000199:Actins / Q000096:biosynthesis; D000803:Angiotensin I / Q000494:pharmacology; D000805:Angiotensin III / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002455:Cell Division; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007700:Kinetics; D019808:Losartan; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000096:biosynthesis / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D000199:Actins; D001713:Biphenyl Compounds; D007093:Imidazoles; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000805:Angiotensin III; D015544:Inositol 1,4,5-Trisphosphate; D000803:Angiotensin I; D019808:Losartan; D002118:Calcium