Role of endothelin ETB receptors in bronchoconstrictor and vasoconstrictor responses in guinea-pigs.
In anesthetized and ventilated guinea-pigs, intravenous injections of endothelin (ET)-1 (0.5 nmol/kg), ET-3 (0.5 nmol/kg), and [Ala1,3,11,15]ET-1 (20 nmol/kg), an ETB-selective receptor agonist, induced bronchoconstrictor and transient vasoconstrictor responses. Only the ET-1-induced transient vasoconstriction was followed by a secondary sustained pressor response. The ETA-selective receptor antagonist, BQ-123 (1 mg/kg i.v.), attenuated only the sustained pressor response. These results indicate that the bronchoconstrictor and transient vasoconstrictor responses to endothelins in guinea-pigs are mediated by ETB receptors, whilst the sustained pressor response is mediated by ETA receptors. The thromboxane A2 receptor antagonist, L-670,596 (0.5 mg/kg, i.v.) and a high dose of BQ-123 (30 mg/kg i.v.) abolished the bronchoconstriction only without affecting the transient pressor response to endothelin isopeptides. These results suggest that the ETB-mediated bronchoconstriction depends on thromboxane A2 formation. The different sensitivity of these ETB-mediated transient responses to BQ-123 suggests the possible existence of distinct ETB receptor subtypes.
Noguchi
K
K
New Drug Discovery Research Laboratories, Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., Japan.
Noguchi
Y
Y
Hirose
H
H
Nishikibe
M
M
Ihara
M
M
Ishikawa
K
K
Yano
M
M
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000595:Amino Acid Sequence; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology*; D002227:Carbazoles / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D017466:Receptors, Endothelin / Q000187:drug effects / Q000502:physiology*; D013931:Thromboxanes / Q000037:antagonists & inhibitors; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D002227:Carbazoles; D016232:Endothelins; D010456:Peptides, Cyclic; D011450:Prostaglandin Endoperoxides, Synthetic; D017466:Receptors, Endothelin; D013931:Thromboxanes; D014662:Vasoconstrictor Agents; C061299:L 670596; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C072247:cyclo(Trp-Asp-Pro-Val-Leu)