title: Subtypes of endothelin ETA and ETB receptors mediating venous smooth muscle contraction.
abstract: In rabbit saphenous vein, endothelin (ET)-1 and ET-3 induced sustained contractions whereas the selective agonists of the ETB receptor, sarafotoxin S6c (STXc) and IRL 1620, induced transient contractions. In the presence of an ETA antagonist, BQ-123, contractions induced by ET-1, STXc and IRL 1620 did not change whereas ET-3 induced only transient contraction. The ETB antagonists, RES-701-1 and IRL 1038, only weakly antagonized the effects of these stimulants. In the muscle pretreated with STXc, neither STXc nor IRL 1620 was effective whereas ET-3 induced sustained contraction at higher concentrations than ET-1. In the muscle pretreated with STXc, BQ-123 weakly antagonized the effect of ET-1 and abolished the effect of ET-3. These results suggest that there are two types of ET receptors; less tachyphylactic and isopeptide-selective ETA receptor, and tachyphylactic and isopeptide-nonselective ETB receptor. The ETA receptors may be further classified as a BQ-123-sensitive ETA1 and a BQ-123-insensitive ETA2 subtypes. The ETB receptors may also be subclassified as the ETB1 and ETB2 subtypes based on the sensitivity to the ETB antagonists.
authors.affiliation: Department of Veterinary Pharmacology, Faculty of Agriculture, University of Tokyo, Japan.
authors.forename: S A
authors.initials: SA
authors.lastname: Sudjarwo
authors.forename: M
authors.initials: M
authors.lastname: Hori
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuda
authors.forename: T
authors.initials: T
authors.lastname: Okada
authors.forename: H
authors.initials: H
authors.lastname: Karaki
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D011817:Rabbits; D017466:Receptors, Endothelin / Q000187:drug effects / Q000502:physiology*; D012501:Saphenous Vein / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology
chemical_list: D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; C074308:sovateltide; C072247:cyclo(Trp-Asp-Pro-Val-Leu)