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. I-125- 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 ET(A) receptor subtype. FR-139317 and BQ-123, two ET(A) antagonists, both inhibited I-125-ET-1 binding. BQ-123 only elicited a partial inhibition. The fraction resistant to BQ-123 did not represent the ET(B) receptor subtype, since no specific I-125-ET-3 binding could be detected. ET-1 and ET-3 were found to stimulate [H-3]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 [H-3]IP. BQ-123 was only a partial inhibitor, whereas FR-139317 totally suppressed ET-1-stimulated production of [H-3]IP. We conclude that human myometrial cells in culture exclusively possess ETA receptor subtypes coupled to phospholipase C.