1999 Fiscal Year Final Research Report Summary
Clinical trial of oxytocin antagonist in preterm labor
| Project/Area Number |
09671725
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Fukuoka University |
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Principal Investigator |
KAWARABAYASHI Tatsuhiko Fukuoka Univ., Sch. Medicine, Professor, 医学部, 教授 (30142350)
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| Project Period (FY) |
1997 – 1999
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| Keywords | Oxytocin / Onset of labor / Preterm labor / Oxytocin antagonist |
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| Research Abstract |
We determined the myometrial oxytocin receptor density and the maternal plasma concentration of oxytocin and progesterone on gestational days 18, 20, and 22 (morning) and at the onset of delivery (day 22 afternoon) in rats with labor at term and at the onset of delivery (day 20 afternoon) in rats in preterm labor induced by the combined use of bilateral ovariectomy and estradiol infection. We also evaluated effected of a nonpeptidyl oxytocin antagonist, L-366, 509, on the initiation of both term and preterm labor. The results were as follows : the number of tritiated oxytocin binding sites in myometrial membranes rapidly increased on gestational day 22 (morning) in rats with term labor. Plasma progesterone level decreased in an inverse fashion. A rapid increase in circulating oxytocin concentration was observed at the onset of delivery in rats in labor at term. Both the plasma oxytocin concentration and the receptor density had the same values in rats with preterm labor as in rats with term labor. L-366, 509 delayed the initiation of labor rats with term and preterm labor in a dose-dependent manner. In conclusion, it is confirmed biochemical and pharmacologically that oxytocin plays an important role in the initiation of both term and preterm labor in rats. The oxytocin antagonist examined was able to delay term and preterm labor, so it might prove useful in clinical practice for the treatment of preterm labor.
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[Publications] Itoh, C., Watanabe, M., Nagamatsu, A., Soeda, S., Kawarabayashi, T., Shimeno, H.: "Two molecular species of oxytocinase (L-cystine aminopeptidase) in human placenta : purification and characterization."Biol. Pharm. Bull.. 20. 20-24 (1997)
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[Publications] Lin, S. -H., Miyata, S., Matsunaga, W., Kawarabayashi, T., Nakashima, T., Kiyohara, T.: "Metabolic mapping or the brain in pregnant, parturient and lactating rates using Fos immunohistochemistry"Brain Res. 787. 226-236 (1998)
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[Publications] Nagata, Y., Honjou, K., Sonoda, M., Makino, I., Tamura, R., Kawarabayashi, T.: "Peri-ovarian adhesions interfere with the diffusion of gonadotrophin into the follicular fluid."Human Reprod. 13. 2072-2076 (1998)
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[Publications] Kobayashi, M., Akahane, M., Minami, K., Moro, M., Ajisawa, Y., Inoue, Y., Kawarabayashi, T.: "Role of oxytocin in the initiation of term and preterm labor : changes in receptor density and plasma oxytocin concentration, and the effect of an oxytocin antagonist, L-366, 509, in rats"Am. J. Obstet. Gynecol. 180. 621-627 (1999)
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[Publications] Makino, Y., Shibata, K., Makino, I., Ono, Y., Kangawa, K., Kawarabayashi, T.: "Expression of adrenomedullin in feto-placental circulation of human normotensive pregnant women and pregnancy-induced hypertensive women."Endocrinology. 140. 5439-5442 (1999)
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[Publications] Tominaga, K., Honda, K., Akahoshi, A., Makino, Y., Kawarabayashi, T., Takano,Y., Kamiya, H: "Substance P causes adhesion of neutrophils to endothelial cells via protein kinase C."Biol. Pharm. Bull.. 22. 1242-1245 (1999)
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[Publications] Okabe, K., Inoue, Y., Kawarabayashi, T., Kaijya, H., Okamoto, F., Soeda, H.: "Physiological significance of hyperpolarization-activated inward currents (Ih) in smooth muscle cells from the circular layers of pregnant rat myometrium."Pflugers-Arch.-Eur. J. Physiol.. 439. 76-85 (1999)
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