Characterization of canine renal endothelin receptor subtypes and their function.
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.
Brooks
D P
DP
SmithKline Beecham Pharmaceuticals, Department of Renal Pharmacology, King of Prussia, Pennsylvania.
DePalma
P D
PD
Pullen
M
M
Nambi
P
P
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
D017466:Receptors, Endothelin