Involvement of endothelin receptor subtypes in human myometrial activity.
We investigated the contribution of endothelin (ET) ETA and ETB receptors to ET-induced contractions of human myometrium and their distribution in cultured myometrial cells. ET-1 was more potent than ET-3 in evoking concentration-dependent increases in smooth muscle tension. A selective ETB agonist, BQ 3020, was inactive in eliciting contractions. In myometrial cell membranes, no specific [125I]ET-3 binding was observed. Inhibition of [125I]ET-1 binding by unlabeled compounds showed the following order of potency: ET-1 = FR 139317 > ET-3 >> S6c. Furthermore, ET-1 increased inositol phosphate (IP) production in a dose-dependent manner. ET-1-induced IP accumulation was totally abolished by FR 139317 (an ETA-selective antagonist) but was not altered by IRL 1038 (an ETB-selective antagonist). These results indicate that only ETA receptors, which mediate ET-1-induced uterine contraction, are present in cultured myometrial cells.
Héluy
V
V
Institut National de la Santé et de la Recherche Médicale, Université René-Descartes, Paris, France.
Fournier
T
T
Cavaillé
F
F
Germain
G
G
Ferré
F
F
Breuiller-Fouché
M
M
D000328:Adult; D002478:Cells, Cultured; D016232:Endothelins / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D006801:Humans; D008875:Middle Aged; D017466:Receptors, Endothelin / Q000145:classification / Q000502:physiology*; D014590:Uterine Contraction / Q000187:drug effects
D016232:Endothelins; D017466:Receptors, Endothelin