PMID- 1415569 OWN - NLM STAT- MEDLINE DCOM- 19921029 LR - 20171213 IS - 0002-9513 (Print) IS - 0002-9513 (Linking) VI - 263 IP - 3 Pt 2 DP - 1992 Sep TI - Angiotensin II receptor subtypes in cultured rat renal mesangial cells. PG - F411-6 AB - The selective angiotensin (ANG II) antagonists losartan (DuP 753) and PD 123319 have been shown to bind selectively to AT1 and AT2 subtypes, respectively. To characterize ANG II receptor subtypes in mesangial cells, washed membranes were incubated with 0.1 to 0.5 nM 125I-ANG II and increasing concentrations of competitors. The inhibition of 125I-ANG II binding by losartan and PD 123319 was biphasic, and LIGAND curve-fitting analysis revealed two populations of specific binding sites. One subpopulation comprised 86% of the total and showed high affinity for ANG II and losartan, but low affinity for the AT2 antagonists PD 123319 and CGP42112A, and thus appear identical to the recently cloned AT1 subtype. The remaining 14% of the sites showed nearly 100-fold lower affinity for losartan and 10,000-fold higher affinity for PD 123319 relative to AT1 sites. However, another AT2-selective antagonist, CGP42112A, showed little affinity for these sites. Both classes of binding sites were inhibited by guanosine 5'-O-(3-thiophosphate) and pertussis toxin treatment. We propose that there are two distinct G protein-coupled ANG II receptor subtypes (AT1A and AT1B) present in renal mesangial cells. FAU - Ernsberger, P AU - Ernsberger P AD - Department of Medicine, Case Western Reserve School of Medicine, Cleveland, Ohio 44106. FAU - Zhou, J AU - Zhou J FAU - Damon, T H AU - Damon TH FAU - Douglas, J G AU - Douglas JG LA - eng GR - HL-22990/HL/NHLBI NIH HHS/United States GR - HL-41618/HL/NHLBI NIH HHS/United States GR - HL-44514/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Am J Physiol JT - The American journal of physiology JID - 0370511 RN - 0 (Angiotensin Receptor Antagonists) RN - 0 (Biphenyl Compounds) RN - 0 (Imidazoles) RN - 0 (Pyridines) RN - 0 (Receptors, Angiotensin) RN - 0 (Tetrazoles) RN - 0 (Virulence Factors, Bordetella) RN - 11128-99-7 (Angiotensin II) RN - 130663-39-7 (PD 123319) RN - 37589-80-3 (Guanosine 5'-O-(3-Thiotriphosphate)) RN - EC 2.4.2.31 (Pertussis Toxin) RN - EC 3.6.1.- (GTP-Binding Proteins) RN - JMS50MPO89 (Losartan) SB - IM MH - Angiotensin II/antagonists & inhibitors/metabolism MH - Angiotensin Receptor Antagonists MH - Animals MH - Binding Sites/drug effects MH - Biphenyl Compounds/pharmacology MH - Cells, Cultured MH - GTP-Binding Proteins/antagonists & inhibitors MH - Glomerular Mesangium/cytology/*metabolism MH - Guanosine 5'-O-(3-Thiotriphosphate)/pharmacology MH - Imidazoles/pharmacology MH - Losartan MH - Pertussis Toxin MH - Pyridines/pharmacology MH - Rats MH - Receptors, Angiotensin/*metabolism MH - Tetrazoles/pharmacology MH - Virulence Factors, Bordetella/pharmacology EDAT- 1992/09/01 00:00 MHDA- 1992/09/01 00:01 CRDT- 1992/09/01 00:00 PHST- 1992/09/01 00:00 [pubmed] PHST- 1992/09/01 00:01 [medline] PHST- 1992/09/01 00:00 [entrez] AID - 10.1152/ajprenal.1992.263.3.F411 [doi] PST - ppublish SO - Am J Physiol. 1992 Sep;263(3 Pt 2):F411-6. doi: 10.1152/ajprenal.1992.263.3.F411.