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Clinical trial of oxytocin antagonist in preterm labor

Research Project

Project/Area Number 09671725
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionFukuoka University

Principal Investigator

KAWARABAYASHI Tatsuhiko  Fukuoka Univ., Sch. Medicine, Professor, 医学部, 教授 (30142350)

Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1997: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsOxytocin / Onset of labor / Preterm labor / Oxytocin antagonist / 切迫早産 / ヒト子宮筋 / オキシトシン受容体 / プロゲステロン
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.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (31 results)

All Other

All Publications (31 results)

  • [Publications] Kawarabayashi, T. et al.: "Effects of oxytocin, prostaglandin Fza and prostaglandin E_2 on intracellular free calcium concentrations of longrtudinal muscle cells isolated from term pregnant rat myometrium"Gynecol. Obstet. Invest.. 43. 145-149 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kawarabayashi, T. et al.: "Changes in responsiveness of freshly isolated longitudinal muscle cells from rat uterus towards oxytocin during gestation : oontractility and calcium signaling"Mol. Cell. Endocrinol.. 128. 77-84 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakao, K. et al.: "Oxytocin enhances action potentials in pregnant human myometrium -A study with microelectrodes"Am. J. Obstet. Gynecol.. 177. 222-228 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Lin. S.-H. et al.: "Metabolic mapping of the brain in pregnant and lactating rats using Fos immunohistochemistry"Brain Res. 787. 226-236 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kobayashi, M. et al.: "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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Okabe, K. et al.: "Physiological significance of hyperpolarization-activated inward currents (Ih) in smoothmuscle cells from the circular layers of pregnam* rat myometrium"Pflugers-Arch. -Eur. J. Physiol.. 439. 76-85 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 瓦林達比古(分担): "分娩の異常:NEW産婦人科学"南江堂. 627 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 瓦林達比古(分担): "子宮収縮:新女性医学大系(正常分娩)"中山書店. 312 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kawarabayashi, T., Shojo, H., Tsukamoto,T.: "Effects of oxytocin, prostaglandin FィイD22αィエD2 and prostaglandin EィイD22ィエD2 on intracellular free calcium concentrations of longitudinal muscle cells isolated from term pregnant rat myometrium."Gynecol. Obstet. Invest.. 43. 145-149 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kawarabayashi, T., Tsukamoto, T., Shojo, H., Nakamura, S., Sugimori, H: "Changes in responsiveness of freshly isolated longitudinal muscle cells from rat uterus towards oxytocin during gestation : contractility and calcium signaling."Mol. Cell. Endocrinol.. 128. 77-84 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakao, K., Inoue, Y., Okabe, K., Kawarabayashi, T., Kitamura, K.: "Oxytocin enhances action potentials in pregnant human myometrium - A study with microelectrodes."Am. J. Obstet. Gynecol.. 177. 222-228 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Makino, I., Shibata ,K., Makino, Y., Kangawa, K., Kawarabayashi, T.: "Adrenomedullin attenuates the hypertension in hypertensive pregnant rats induced by NィイD2GィエD2-nitro-L-arginine methyl ester."Eur. J. Pharmac. 371. 159-167 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Makino,I..,Shibata,K.,Makino,Y.,Kangawa,K.,Kawarabayashi,T.: "Adrenomedullin attenuates the hypertension in hypertensive pregnant rats induced by N^G-nitro-L-arginine methyl ester"European Journal of Pharmacology. 371. 159-167 (1999)

    • Related Report
      1999 Annual Research Report
  • [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 hyper-tensive women"Endocrinology. 140. 5439-5442 (1999)

    • Related Report
      1999 Annual Research Report
  • [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"Biological & Pharmaceutical Bulletin. 22. 1242-1245 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Okabe,K.,Inoue,Y.,Kawarabayashi,T.,Kajiya,H.,Okamoto,F.,Soeda,H.: "Physiological significance of hyperpolarization-activated inward currents(In)in smooth muscle cells from the circular layers of pregnant rat myometrium"Pflugers Arch-Eur J Physiol. 439. 76-85 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Makino,I.,Shibata,K.,Makino,Y.,Kangawa.K.,Kawarabayashi,T.: "Potentiation of the hypotensive effect of adrenomedullin in pregnant rats."European Journal of Pharmacology. 385. 129-136 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Lin S. -H. et al. (Kawarabayashi T): "Metabolic mapping of the brain in pregnant, parturient and lactating rats using Fos immunohistochemistry" Brain Research. 787. 226-236 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 瓦林 達比古: "オキシトシン産生調節機構とその生理作用" 日産雑誌. 50(8). 599-604 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kobayashi M. et al. (Kawarabayashi T): "Role of oxytocin in the initiation of term and preterm labor:changes in receptor density and plasma oxytocin concentiation and the effect of an oxytocin antagonist, L-366 ,509 in rats." Am.J.Obstet.Gynecol.(in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kawarabayashi T,et al.: "Effects of oxytocin,prostaglandin F_2α and prostaglondin E_2 on intracellular free calcium concentrations of longitudinal muscle cells isolated from term pregonant rat myometrium." Gynecol.Obstet.Invest.43. 145-149 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kawarabayashi T,et al.: "changes in responsiveness of freshly is odated longitudinal muscle cells from rat utenis towared oxytocin during gestation:controctility and calcium sugnaling." Mol.Cell.Endocrinol.128. 77-84 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Itoh S,et al.(Kawarabayashi T): "Two molecular species of oxytocinase(L-cystine aminopeptidase)in human placenta:purification and characterization." Biol.Pharm.Bull.20. 20-24 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nakao K,et al.: "Oxytocin enhances action potentials in pregnant human myometrium-A study with microelectrodes." Am.J.Obstet.Gynecol.177. 222-228 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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