Endothelin ETA receptors mediate human uterine smooth muscle contraction.
Receptors mediating endothelin-induced contraction of myometrium were investigated in the human uterus. Endothelin-1 and endothelin-3 (10 pM to 0.3 microM) caused concentration-dependent contraction of myometrial strips. Endothelin-1 was approximately ten times more potent than endothelin-3, with pD2 values of 8.24 and 7.20, respectively. By contrast, two endothelin ETB receptor selective agonist, BQ 3020 (N-acetyl-[Ala11,15]endothelin-1-(6-21) and sarafotoxin 6c (up to 0.3 microM), did not induce contraction of human myometrium. The endothelin ETA receptor selective antagonist, FR139317 (1-hexahydroazepino-CO-Leu-D-Trp(CH3)-D-(2-pyridyl)alanine) (0.1, 0.3 and 1 microM), competitively antagonized the endothelin-1-elicited contraction, with a pA2 value of 7.10, whereas another endothelin ETA receptor-selective blocking drug, BQ 123 [cyclo(-D-Trp-D-Asp-Pro-D-Val-Leu)], behaved as a non-competitive antagonist. Pretreatment of myometrial strips with an endothelin ETB receptor selective antagonist, IRL 1038 ([Cys11-Cys15]endothelin-1-(11-21)), had no effect on contractions induced by endothelin-1. All these data indicate that only endothelin ETA receptors mediate endothelin-1-induced contractions of human myometrium.
Héluy
V
V
Institut National de la Santé et de la Recherche Médicale, U.361, Université René-Descartes, Paris, France.
Germain
G
G
Fournier
T
T
Ferré
F
F
Breuiller-Fouché
M
M
D000328:Adult; D000595:Amino Acid Sequence; D001381:Azepines / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008875:Middle Aged; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000494:pharmacology; D017466:Receptors, Endothelin / Q000502:physiology*; D014590:Uterine Contraction / Q000187:drug effects
D001381:Azepines; D016232:Endothelins; D007211:Indoles; D010456:Peptides, Cyclic; D017466:Receptors, Endothelin; C079574:FR 139317; C072247:cyclo(Trp-Asp-Pro-Val-Leu)