title: Multiple subtypes of endothelin receptors in human and porcine tissues: characterization by ligand binding, affinity labeling, and regional distribution.
abstract: To characterize the properties and the distribution of endothelin (ET) receptor subtypes, we have examined the ligand selectivity and the molecular weight (Mr) of [125I]ET-1 and [125I]ET-3 binding sites in various tissues of human and pigs. ET-1 and ET-2 showed almost identical potencies in displacing the bound [125I]ET-1 in all of the tissues examined. ET-3, sarafotoxin S6b (SRTX-b), and sarafotoxin S6C (SRTX-c) displaced the [125I]ET-1 with nearly the same sensitivity as ET-1 (IC50 = 0.07-3.0 nM) in brain, kidney, liver, and adrenal, whereas the three peptides showed very weak competition (IC50 = 40-500 nM) against [125I]ET-1 binding in atria, aorta, lung, stomach, and uterus. The Bmax value for [125I]ET-3 was 83% of that for [125I]ET-1 in human liver membranes, whereas the Bmax for [125I]ET-3 was only 12% of that for [125I]ET-1 in human atrial membranes. [125I]ET-3 bound to liver and atrial membranes was displaced by ET/SRTX isopeptides almost equipotently. Two proteins with Mr of 110 and 50 kDa were specifically affinity-labeled with [125I]ET-1 in porcine lung membranes. The above findings indicated that two distinct subclasses of ET receptors, namely ET-1/ET-2-specific and ET/SRT family common receptors, were distributed in various proportions in mammalian tissues.
authors.affiliation: Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Takayanagi
authors.forename: K
authors.initials: K
authors.lastname: Ohnaka
authors.forename: C
authors.initials: C
authors.lastname: Takasaki
authors.forename: M
authors.initials: M
authors.lastname: Ohashi
authors.forename: H
authors.initials: H
authors.lastname: Nawata
mesh_terms: D000345:Affinity Labels; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D016232:Endothelins / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008970:Molecular Weight; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017466:Receptors, Endothelin; D013552:Swine; D014018:Tissue Distribution; D014757:Viper Venoms / Q000494:pharmacology
chemical_list: D000345:Affinity Labels; D016232:Endothelins; D008024:Ligands; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; D014757:Viper Venoms; C057354:sarafotoxins s6