title: Characterization of canine renal endothelin receptor subtypes and their function.
abstract: Binding and renal functional studies were conducted to characterize endothelin (ET) receptors in the dog kidney. Binding studies that were performed in renal cortical membranes by using [125I]-ET-1 and [125I]-ET-3 and the ETA- and ETB-selective ligands, BQ123 (cyclo [D-Trp-D-Asp-L-Pro-D-Val-L-Leu]) and sarafotoxin 6c (S6c), respectively, revealed that the ratios of ETA to ETB receptors in cortical, medullary and papillary membranes were 22:78, 39:61 and 50:50, respectively. In vivo studies in the anesthetized dog demonstrated that an intrarenal artery infusion of ET-1 (0.3-10 ng kg-1 min-1) resulted in a dose-dependent decrease in renal blood flow (RBF) and glomerular filtration rate (GFR). At a dose of 10 ng kg-1 min-1 of ET-1, RBF and GFR decreased by 82 +/- 6% and 89 +/- 6%, respectively. An infusion of BQ123 (10 micrograms kg-1 min-1) into the renal artery resulted in a significant inhibition of the ET-1-induced renal vasoconstriction. At identical doses as ET-1, S6c had little effect on either RBF (-3 +/- 6%) or GFR (-6 +/- 16%). ET-1 decreased urine flow and had little effect on fractional sodium excretion, whereas S6c increased both urine flow and fractional sodium excretion. These data indicate that ET-1-induced renal vasoconstriction in the dog is mediated by ETA receptors; however, ETB receptor stimulation may inhibit sodium reabsorption.
authors.affiliation: SmithKline Beecham Pharmaceuticals, Department of Renal Pharmacology, King of Prussia, Pennsylvania.
authors.forename: D P
authors.initials: DP
authors.lastname: Brooks
authors.forename: P D
authors.initials: PD
authors.lastname: DePalma
authors.forename: M
authors.initials: M
authors.lastname: Pullen
authors.forename: P
authors.initials: P
authors.lastname: Nambi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004285:Dogs; D005260:Female; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000098:blood supply / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D017466:Receptors, Endothelin / Q000145:classification / Q000378:metabolism*; D012039:Regional Blood Flow
chemical_list: D017466:Receptors, Endothelin