Characterization of type A endothelin receptors in cultured human myometrial cells.
The aim of the present study was to characterize endothelin (ET)-receptors in human myometrial cells in culture. 125I-labeled ET-1 binding to myometrial cells was specific and saturable, with a dissociation constant of 64.2 +/- 12.8 pM. Competition binding studies showed the following order of potency: ET-1 > ET-3, which is consistent with the presence of the ETA receptor subtype. FR-139317 and BQ-123, two ETA antagonists, both inhibited 125I-ET-1 binding. BQ-123 only elicited a partial inhibition. The fraction resistant to BQ-123 did not represent the ETB receptor subtype, since no specific 125I-ET-3 binding could be detected. ET-1 and ET-3 were found to stimulate [3H]inositol phosphate (IP) accumulation in cultured myometrial cells, with corresponding half-maximal effective concentration values of 0.26 +/- 0.04 and 87 +/- 17 nM, respectively. Both ETA antagonists inhibited ET-1-induced accumulation of [3H]IP. BQ-123 was only a partial inhibitor, whereas FR-139317 totally suppressed ET-1-stimulated production of [3H]IP. We conclude that human myometrial cells in culture exclusively possess ETA receptor subtypes coupled to phospholipase C.
Héluy
V
V
Institut National de la Santé et de la Recherche Médicale Unité 361, Maternité Baudelocque, Paris, France.
Breuiller-Fouché
M
M
Cavaillé
F
F
Fournier
T
T
Ferré
F
F
D000328:Adult; D002478:Cells, Cultured; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism; D009215:Myometrium / Q000166:cytology / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D011869:Radioligand Assay; D017466:Receptors, Endothelin / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D016232:Endothelins; D010716:Phosphatidylinositols; D017466:Receptors, Endothelin; D010566:Virulence Factors, Bordetella