title: Binding of 125I-endothelin-1 and 125I-endothelin-3 in rabbit saphenous vein: evidence for an atypical ET binding component.
abstract: Recent investigations have confirmed the presence of vasoconstrictory endothelinB (ETB) receptors in several tissues, including the rabbit saphenous vein (RSV). To determine the molecular nature of the ET receptor subtypes in RSV, radioligand-receptor binding with selective ligands was conducted. ET-1 inhibited 125I-ET-1 binding to RSV in a monophasic manner with an inhibition constant (Ki) of 0.08 +/- 0.03 nM. Inhibition of 125I-ET-1 binding by ET-3 or the ETA-selective peptide BQ-123 resulted in markedly biphasic inhibition curves with Ki values of 0.4 +/- 0.1 nM (36% of total sites)/37 +/- 10 nM (64% of total sites) for ET-3 and 10.4 +/- 1.9 nM (70%)/3.2 +/- 0.9 microM (30%) for BQ-123. The correspondence of high-affinity binding sites for BQ-123 with low-affinity binding sites for ET-3 agrees with the suggestion that 70% of the 125I-ET-1 binding sites in this tissue are ETA receptors. To further investigate the nature of the ET-B (non-ET-A) binding sites in RSV, 125I-ET-3 competition binding was conducted. ET-1 and BQ-123 inhibited 125I-ET-3 binding in RSV with Ki values of 40 +/- 7 pM and 7.2 microM, respectively, while ET-3 and the ETB receptor-selective agonist sarafotoxin S6c (S6c) inhibition curves were best fit to two-site models. Resultant Ki values for ET-3 and S6c were 50 pM (71%)/4 pM (29%) and 0.3 nM (76%)/115 nM (24%).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Cardiovascular Biochemistry, Pharmaceutical Research Institute, Princeton, NJ 08543-4000.
authors.forename: E C
authors.initials: EC
authors.lastname: Liu
authors.forename: H
authors.initials: H
authors.lastname: Monshizadegan
authors.forename: C C
authors.initials: CC
authors.lastname: Chao
authors.forename: J
authors.initials: J
authors.lastname: Lynch
authors.forename: S M
authors.initials: SM
authors.lastname: Fisher
authors.forename: P M
authors.initials: PM
authors.lastname: Rose
authors.forename: M L
authors.initials: ML
authors.lastname: Webb
mesh_terms: D000818:Animals; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000378:metabolism* / Q000494:pharmacology; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000494:pharmacology; D011817:Rabbits; D011869:Radioligand Assay; D017466:Receptors, Endothelin / Q000378:metabolism*; D012501:Saphenous Vein / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology
chemical_list: D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D007457:Iodine Radioisotopes; D010456:Peptides, Cyclic; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; C072247:cyclo(Trp-Asp-Pro-Val-Leu)