THE MECHANISM OF MYOMETRIAL CONTRACTIONS INDUCED BY ENDOTHELIN-1 IN RAT

Experiments were performed to characterize endothelin-1-induced contra ctions and the role of endothelin (ET) receptor subtypes in rat myomet rium. The binding sites of [I-125]-ET-1 were saturable with high affin ity. Scatchard plot analysis revealed that ET-1 binding sites in the m yometrium constituted a single population, The dissociation equilibriu m constant (K-d) and the maximum binding sites (B-max) were determined to be 48.9 +/- 3.0 pM and 1364.0 +/- 210.3 fmol/mg protein respective ly, Specific [I-125]-ET-1 binding was inhibited completely by unlabell ed ET-1 and Ro 46-2005 (mixed-type ET receptor antagonist), but not fu lly (90.7 +/- 1.4%) by BQ 123 (a selective ETA receptor antagonist), a nd not at all by RES 701-1 (a selective ETB receptor antagonist), ET-1 induced myometrial contractions were composed of two types, an increa se in resting tone and rhythmic contractions, These contractions were inhibited by BQ 123 and Ro 46-2005, but not by RES 701-1, ET-1-induced contractions were greatly reduced in Ca2+-free Krebs' solution. Nifed ipine abolished the rhythmic contractions without affecting the increa se in resting tone, These results suggest that ETA receptors are predo minantly localized in rat myometrium and that excitation of ETA recept ors evokes two types of contractions by increasing the cytoplasmic Ca2 + concentration.