Molecular Human Reproduction, Vol. 5, No. 3, 270-276,
March 1999
© 1999 European Society of Human Reproduction and Embryology
Gestational changes in endothelin-1-induced receptors and myometrial contractions in rat
1 Department of Obstetrics and Gynecology, Faculty of Medicine, Tokyo Medical and Dental University, 1–5–45 Yushima, Bunkyo-ku, Tokyo 113-8519, and 2 Department of Medicinal Chemistry, Institute for Medical and Dental Engineering, Tokyo Medical and Dental University, 2–3–10 Surugadai, Kanda, Chiyoda-ku, Tokyo 101-0062, Japan
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 [125I]-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.
endothelin-1/ETA receptor/ETB receptor/gestation/myometrial contraction
3 To whom correspondence should be addressed
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