title: Multiple subtypes of endothelin receptors in porcine tissues: characterization by ligand binding, affinity labeling and regional distribution.
abstract: To clarify the existence and the distribution of endothelin (ET) receptor subtypes, we have examined the pharmacological properties and the molecular weight (Mr) of 125I-ET-1 and 125I-ET-3 binding sites in various tissues of pigs. ET-1 and ET-2 showed almost identical potencies in displacing the bound 125I-ET-1 in all the tissues examined. ET-3, sarafotoxin S6b (SRT-b) and sarafotoxin S6c (SRT-c) displaced the 125I-ET-1 with the same sensitivity as ET-1 (IC50 = 0.1-1.4 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 cardiac atria, aorta, lung, stomach and uterus. The computer analyses of the binding data suggested the presence of high (Kd1 = 0.04-0.29 nM) and low (Kd2 = 60-190 nM) affinity binding sites for ET-3 and SRT-b in lung and stomach. 125I-ET-3 bound to the high affinity sites in lung and stomach was displaced by ET/SRT isopeptides almost equipotently. Two proteins with Mr of 47,000 and 35,000 were affinity-labeled with 125I-ET-1 in cerebellum, while a protein with Mr of 123,000, in addition to the two proteins, was predominantly labeled in lung. The above findings indicated that two distinct subclasses of ET receptors, namely, ET-1-specific and ET/SRT family-common receptors were distributed in various proportions in mammalian tissues, and suggested that their molecular forms are also different.
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 / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D016232:Endothelins / Q000378:metabolism*; D008024:Ligands; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009928:Organ Specificity; D011956:Receptors, Cell Surface / Q000145:classification* / Q000378:metabolism; D017466:Receptors, Endothelin; D012689:Sequence Homology, Nucleic Acid; D013552:Swine / Q000378:metabolism*; D014757:Viper Venoms / Q000378:metabolism
chemical_list: D000345:Affinity Labels; D016232:Endothelins; D008024:Ligands; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; D014757:Viper Venoms; C057354:sarafotoxins s6