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Gestational changes in endothelin-1-induced receptors and myometrial contractions in rat.

The present experiments were performed to characterize the gestational changes in endothelin (ET)-1-induced myometrial contractions and ET receptors in rat. ET-1-induced contractions were composed of two types: increases in resting tone and rhythmic contractions. The increase in resting tone was decreased at 7 days of gestation, but increased at 20 days. The increase in amplitude and frequency of rhythmic contractions remained unchanged during days 7-14 of gestation. Continuous rhythmic contractions were not produced by ET-1 near the term. Both contractions were inhibited by the antagonists BQ 123 and Ro 46-2005 but not by RES 701-1 or BQ 788. In binding studies, total binding sites of [1251]-ET-1 were unchanged, however higher affinity binding sites appeared during pregnancy in addition to the lower affinity sites. The specific [125I]-ET-1 binding in non-pregnant and pregnant myometrium was completely inhibited by unlabelled ET-1 and Ro 46-2005. In contrast, the proportion which was inhibited by BQ 123 was decreased during pregnancy. In conclusion, characteristic gestational changes were the augmentation of ET-1-induced increased resting tone near term, and the appearance of high affinity ET-1 binding sites and an increase in BQ 123-resistant ET-1 binding sites during pregnancy. Further investigations are needed to understand the physiological role of these changes.