A novel subtype of endothelin B receptor mediating contraction in swine pulmonary vein.
Effects of agonists and antagonists of endothelin (ET) receptors were examined in swine pulmonary artery and vein and in rabbit saphenous vein. ET-1, but not ETB receptor agonists, sarafotoxin S6c (STXc) and IRL 1620, induced contraction in pulmonary artery. This effect was inhibited by the ETA receptor antagonists, BQ-123 and FR139317, but not by the ETB receptor antagonist, IRL 1038. Pulmonary artery precontracted by norepinephrine was relaxed by ET-3 in an endothelium-dependent manner. This relaxation was inhibited by IRL 1038 but not by BQ-123. In pulmonary vein, ET-1, ET-3, STXc and IRL 1620 induced contractions at a similar concentration range. ET-1 induced contraction also in saphenous vein. These contractions were not inhibited by BQ-123, FR139317 or IRL 1038. These results suggest that the isopeptide-selective ETA receptor mediates contraction in swine pulmonary artery whereas the isopeptide-nonselective ETB receptor mediates release of endothelium-derived relaxing factor. In contrast, contractions in the veins may be mediated by a novel subtype of isopeptide-nonselective ETB receptor which is not inhibited by IRL 1038.
Sudjarwo
S A
SA
Department of Veterinary Pharmacology, Faculty of Agriculture, University of Tokyo, Japan.
Hori
M
M
Takai
M
M
Urade
Y
Y
Okada
T
T
Karaki
H
H
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000494:pharmacology / Q000502:physiology; D007211:Indoles / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D011667:Pulmonary Veins / Q000187:drug effects* / Q000502:physiology*; D011817:Rabbits; D017466:Receptors, Endothelin / Q000145:classification / Q000187:drug effects* / Q000502:physiology*; D012501:Saphenous Vein / Q000187:drug effects / Q000502:physiology; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology
D001381:Azepines; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D007211:Indoles; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; C074308:sovateltide; C079574:FR 139317; C072247:cyclo(Trp-Asp-Pro-Val-Leu)