CHARACTERIZATION OF I-125 ENDOTHELIN-1 BINDING TO RAT AND RABBIT RENAL MICROVASCULALURE

We characterized I-125-ET-1 binding to renal microvascular membranes isolated from the rat, a species showing ET(B) receptor-mediated renal vasoconstriction, and the rabbit in which ET-induced renal vasoconstriction is mediated by the ET(A) receptor. In both species, I-125-ET-1 bound in a manner consistent with a single high-affinity site. Scatchard analysis yielded K-d and B-max values of 20.1 +/- 0.4 pM and 1343 +/- 64 fmol/mg for the rat and 21.5 +/- 0.9 pM and 810 +/- 64 fmol/mg for the rabbit. Competition binding studies with several selective (sarafotoxin 6c, BQ123) and mixed ET(A)/ET(B) (SE 209670) ET receptor ligands showed that the renal microvasculature from both species contain ET(A) and ET(B) receptors in a proportion of 40:60. In the rat, the proportion of ET(A) receptors was higher in the microvasculature than in glomeruli and inner medullary collecting duct cells both of which contained > 80% ET(B) receptors. In the rabbit, the proportion of ET(A)/ET(B) receptors was similar in the microvasculature and inner medullary collecting duct cells (similar to 40:60), whereas glomeruli contained 80% ET(B) receptors. Although ET-induced renal vasoconstriction in the rat and rabbit is mediated by different ET receptor subtypes, the proportion of ET(A) to ET(B) receptors is the same in the renal microvasculature from these species.