Identification of a novel endothelin receptor in Xenopus laevis liver.
Membranes prepared from Xenopus liver displayed high density of high affinity endothelin (ET) binding sites. These sites have the same affinity for [125I] ET-1 and [125I] ET-3. Scatchard analysis of the specific binding from saturation binding experiments revealed an apparent dissociation constant (Kd) of 93.1 and 70.9 pM and maximum binding (Bmax) of 602 and 651 fmol/mg protein for [125I] ET-1 and [125I] ET-3, respectively. Competition binding experiments using [125I] ET-1 and unlabelled ET-1, ET-3, S6c, and BQ123 indicated that ET-1 and ET-3 were the most potent in displacing [125I] ET-1 binding from these membranes (IC50 1 and 0.3 nM, respectively), whereas S6c BQ123, selective for ETB and ETA receptors, respectively, did not have any inhibitory effect up to 1 microM. These data clearly indicate that the ET receptors present in Xenopus liver membranes belong to a new subtype of ET receptor. Because it resembled mammalian ETB receptors in its affinities for ET-1 and ET-3, we propose that this receptor be called the ETBX receptor.
Nambi
P
P
Department of Renal Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939.
Pullen
M
M
Kumar
C
C
D000818:Animals; D001667:Binding, Competitive; D016232:Endothelins / Q000378:metabolism / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D008099:Liver / Q000378:metabolism*; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D011869:Radioligand Assay; D017466:Receptors, Endothelin / Q000378:metabolism*; D014982:Xenopus laevis
D016232:Endothelins; D007457:Iodine Radioisotopes; D017466:Receptors, Endothelin