Identification and function of putative ETB receptor subtypes in the dog kidney.
Binding studies performed in dog kidney, lung, and spleen using [125I]endothelin (ET) 3 and a series of ETB-selective ligands indicated the presence of two subtypes of ETB receptors, an IRL-1620-sensitive (putative ETB1) and an IRL-1620-insensitive (putative ETB2) receptor. The IRL-1620-sensitive (but not IRL-1620-insensitive) ETB receptors displayed similar pharmacology to the cloned human ETB receptor and a high affinity for the ETB receptor antagonist RES-701. ETB1 receptors predominated in the dog kidney and lung and ETB2 receptors predominated in the dog spleen. Stimulation of ETB receptors in dogs in vivo inhibited sodium reabsorption, as ET-1 infusion in the presence of the ETA antagonist BQ123, but not the mixed ETA/ETB receptor antagonist, (+/-)SB 209670, resulted in increased sodium excretion. Furthermore, infusion of the ETB-selective agonist Sarafotoxin S6c (S6c) resulted in an increase in sodium excretion, a response that was attenuated by infusion of RES-701. These data indicate that the putative ETB1 receptor may mediate ET-induced inhibition of tubule sodium reabsorption in the dog. In addition, we observed no putative ETB2 receptor-mediated renal vasoconstriction, consistent with the apparent low abundance of this subtype in the dog kidney.
Brooks
D P
DP
Department of Renal Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406-0939, USA.
DePalma
P D
PD
Pullen
M
M
Gellai
M
M
Nambi
P
P
D000818:Animals; D004285:Dogs; D016232:Endothelins / Q000494:pharmacology; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000145:classification / Q000502:physiology*; D012964:Sodium / Q000378:metabolism; D014757:Viper Venoms / Q000494:pharmacology
D016232:Endothelins; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D014757:Viper Venoms; C057354:sarafotoxins s6; C074308:sovateltide; D012964:Sodium; C072247:cyclo(Trp-Asp-Pro-Val-Leu)