Subtypes of endothelin ETA and ETB receptors mediating tracheal smooth muscle contraction.
In the isolated rabbit trachea, endothelin (ET)-1, ET-3 and the selective ETB receptor agonists, IRL 1620 and sarafotoxin S6c (STXc), induced contraction with EC50 of 2-9 nM. An ETA1 receptor antagonist, BQ-123, was ineffective whereas desensitization of the ETB receptor strongly antagonized the effect of ET-3, IRL 1620 and STXc. An ETB1 receptor antagonist, RES-701-1, antagonized the effects of ET-3 and IRL 1620 whereas the effect of STXc was antagonized by an ETB2 receptor antagonist, BQ-788. In the ETB-desensitized trachea, only ET-1 induced large contraction that was partially antagonized by BQ-123. These results suggest that ET induces tracheal contraction by activating multiple ET receptors: the ET-1-selective ETA (BQ-123-sensitive ETA1 and insensitive ETA2 subtypes) and the isopeptide-nonselective ETB receptors (RES-701-1-sensitive ETB1 and insensitive ETB2 subtypes).
Yoneyama
T
T
Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, University of Tokyo, Japan.
Hori
M
M
Makatani
M
M
Yamamura
T
T
Tanaka
T
T
Matsuda
Y
Y
Karaki
H
H
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; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D011817:Rabbits; D017466:Receptors, Endothelin / Q000819:agonists / Q000502:physiology*; D014132:Trachea / Q000187:drug effects / Q000502:physiology*; D014757:Viper Venoms / Q000494:pharmacology
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D010446:Peptide Fragments; D017466:Receptors, Endothelin; D014757:Viper Venoms; C057354:sarafotoxins s6; C074308:sovateltide