IDENTIFICATION AND FUNCTION OF PUTATIVE ET(B) RECEPTOR SUBTYPES IN THE DOG KIDNEY

Binding studies performed in dog kidney, lung, and spleen using [I-125 ]endothelin (ET) 3 and a series of ET(B)-selective ligands indicated t he presence of two subtypes of ET(B) receptors, an IRL-1620-sensitive (putative ET(B1)) and an IRL-1620-insensitive (putative ET(B2)) recept or. The IRL-1620-sensitive (but not IRL-1620-insensitive) ET(B) recept ors displayed similar pharmacology to the cloned human ET(B) receptor and a high affinity for the ET(B) receptor antagonist RES-701. ET(B1) receptors predominated in the dog kidney and lung and ET(B2) receptors predominated in the dog spleen. Stimulation of ET(B) receptors in dog s in vivo inhibited sodium reabsorption, as ET-1 infusion in the prese nce of the ET(A) antagonist BQ123, but not the mixed ET(A)/ET(B) recep tor antagonist, (+/-)SB 209670, resulted in increased sodium excretion . Furthermore, infusion of the ET(B)-selective agonist Sarafotoxin S6c (S6c) resulted in an increase in sodium excretion, a response that wa s attenuated by infusion of RES-701. These data indicate that the puta tive ET(B1) receptor may mediate ET-induced inhibition of tubule sodiu m reabsorption in the dog. In addition, we observed no putative ET(B2) receptor-mediated renal vasoconstriction, consistent with the apparen t low abundance of this subtype in the dog kidney.