Endothelin(A) receptors in human uterine leiomyomas

Objective: To determine if there are endothelin receptors on human uterine leiomyomas. Methods: Samples of leiomyomas from eight patients were analyzed for [iodine (I) -125]endothelin-1 binding. Several subtype-selective ligands were used to determine the endothelin receptor population. Results: Binding of [¹²⁵I]endothelin-1 to uterine leiomyoma membranes was specific and saturable, with a mean ± dissociation constant 85.5 ± 8.4 pM. Competition binding studies showed that the order of potency was endothelin- 1 > endothelin-3, which was consistent with the presence of the endothelin(A) receptor subtype. Binding of [¹²⁵I]endothelin-1 was displaced by an endothelin(A)-selective antagonist, but not by sarafotoxin 6c, an endothelin(B)-selective agonist. An endothelin(B)-selective ligand was not specifically bound to leiomyoma. Conclusion: These results indicate that only endothelin(A) receptors are present in human uterine leiomyomas. We speculate that endothelin-1 may act through these endothelin(A) receptors to influence the development or regulation of hypertrophy and proliferation of the human myometrium during pregnancy and in uterine disorders like leiomyomas.