• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

1993 Fiscal Year Final Research Report Summary

Standardization and problems to measure prostanoids in the biological fluid.

Research Project

Project/Area Number 03557039
Research Category

Grant-in-Aid for Developmental Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Circulatory organs internal medicine
Research InstitutionTOHOKU UNIVERSITY

Principal Investigator

ABE Keishi  Tohoku University School of Medicine, The Second Department of Internal Medicine, Professor, 医学部, 教授 (60004777)

Co-Investigator(Kenkyū-buntansha) MIZUGAKI Mitinao  Tohoku University School of Medicine, Department of Pharmacy, Professor, 医学部・附属病院, 教授 (60004595)
YAMAMOTO Syuzo  Tokushima University, School of Medicine, Department of Biochemistry, Professor, 医学部, 教授 (50025607)
MUROTA Seiitsu  Tokyo Medical and Dental University, School of Dentistry, Professor, 歯学部, 教授 (50072989)
OUTI Kazuo  Tohoku University, Department of Pharmacy, Professor, 薬学部, 教授 (20006357)
KATORI Makoto  Kitasato University School of Medicine, Department of Pharmacology, Professor, 医学部, 教授 (50050365)
Project Period (FY) 1991 – 1993
KeywordsProstacyclin / Thromboxane A_2 / 11-dehydro-thromboxane B_2 / 2, 3-dinor-6-keto-prostaglandin F_1alpha / Hypertension / Toxemia of pregnancy / Inflammation / Measurement
Research Abstract

The method to measure 11-dehydro-thromboxane A_2(TXA_2) in the biological fluid was established by the previous research project. In this following project we performed the clinical application of this method in various human diseases as well as animal models of diseases. Over productions of TXA_2 were suspected in patients with myocardial infarction, cerebral infarction, diabetes mellitus, toxemia of pregnancy and bronchial asthma who showed higher urinary excretions of 11-dehydro-TXB_2, Physiological and pathophysiological roles of TXA_2 were elucidated. Furthermore, various immunoaffinity column and HPLC separation method were developed for the clean up of eicosanoids from the biological fluids and the HPLC-laser system to detect the small amount of eicosanoids was also developed.
On the other hand, EIA kit for 2, 3-dinor-6-keto-prostaglandin (PG)F_1alpha, the stable metabolite of prostacyclin (PGI_2) was developed and we shared in the work for the standardization and clinical applic … More ation of this method. The separation of 2, 3-dinor-6-keto-PGF_1alpha from biological fluid was needed by either immunoaffinity column using anti-6-keto-PGF_1alpha antibody or anti-2, 3-dinor-6-keto-PGF_1alpha antibody or by HPLC before the measurement by EIA.Urinary excretion of 2, 3-dinor-6-keto-PGF_1alpha in man was about 100-400 pg/mg creatinine measured either by EIA or by GC/SIM method. There were no sex related differences and urinary levels were affected mainly by the systemic production rate rather than the renal production rate. Thus the 2, 3-dinor-6-keto-PGF_1alpha seems suitable as the index of systemic production rate of PGI_2. This method was useful to measure the levels in the tissue culture media and in the biological fluid from inflammatory tissue. We also applied clinically to measure the urinary excretion of levels in patients with hypertension, diabetes mellitus and toxemia of pregnancy. The establishment of the measurement of major stable metabolites of TXA_2 and PGI_2, in turn, made it possible to clarify the production balance between TXA_2 and PGI_2 in various diseases. Surplus TXA_2 production than PGI_2 was found in patients with essential hypertension as well as diabetes mellitus.
Thus, most important problems to measure TXA_2 and PGI_2 in the biological fluid was dissolved by these projects and these methods seems to be useful tools to clarify the pathphysiological roles of TXA_2 and PGI_2 in man. Less

  • Research Products

    (43 results)

All Other

All Publications (43 results)

  • [Publications] M.Katori and M.Kawamura: "Multiple effects of eicosapentaenoic acid on the arachidonic metabolism in human platelets." Advances in Polyunsaturated Fatty Acid Research. 87-90

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Hiramatsu,Y.Hayashi,et al.: "PGs LTs and essential fatty acids." (in press). (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] I.Sato,K.Kaji,I.Morita,et al.: "Augmentation of endothelin-1,prostacyclin and thromboxane A_2 secretion associated with in vitro ageing in cultured human umbilical vein endothelial cells." Mechanisms of Ageing and Development. 71. 73-84 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Sato,H.Seki and H.Sakamoto.: "Role of prostaglandins in pregnancy-induced hypertension." Ame.J.Kidney.Diseases. 17(2). 133-138 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 渡邉雅子、渡邉孝則、山田将輝 他: "PAF精製用イムノアフィニティーミニカラムを活用したPAFの測定-thapsigarginによるPAF産生亢進とdexamethasoneの効果-" 炎症. 14(1). 25-30 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] W.Takasaki,A.Nakagawa,F.Asai,et al.: "Superiority of plasma 11-dehydro-TXB_2 to TXB_2 as an index of in vivo TX formation in rabbits after dosing of CS-518,a TX synthase inhibitor." Thromb.Res.71(1). 69-76 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Majima, O.Yoshida, H.Mihara, T.Muto, S.Mizogami, Y.Kuribayashi, M.Katori and S.Ohishi.: "High sensitivity to salt in kininogen-deficient Brown Norway Katholiek rats." Hypertension. 22(5). 705-714 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Hashimoto, Y.Shiozaki and M.Katori.: "Immediate inhibitory effect of methylprednisolone suleptanate (U-67590A) on antigen-induced cutaneous and airway anaphylactic responses in guinea-pigs." Br.J.Pharmacol. 108. 604-612 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Majima, N.Sunahara, Y.Harada and M.Katori.: "Detection of the degradation products of bradykinin by enzyme immunoassays as markers for the release of kinin in vivo." Biochemical Pharmacology. 45(3). 559-567 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Majima, C.Shima, M.Saito, Y.Kuribayashi, M.Katori and T.Aoyagi.: "Poststatin, a novel inhibitor of bradykinin-degrading enzymes in rat urine." Eur.J.Pharmacol. 232. 181-190 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Kawamura, A.Huang, Y.Harada and M.Katori.: "Activation of phospholipase C as a promary target of the thromboxane A_2-mediated amplification mechanism in thrombin-induced rabbit platelet activation." Platelets. 5. 20-28 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Katori and M.Kawamura. (Eds.T.Yasugi, et al.): "Multiple effects of eicosapentaenoic acid on the arachidonic metabolism in human platelets." Advances in Polyunsaturated Fatty Acid Research. 87-90 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Katori, T.Ohno and K.Nishiyama.: "Interaction of substance P and leukotriene C_4 in ethanolind-used mucosal injury of rat stomach." Regulatory Peptides. 46. 241-243 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Hatanaka and M.Katori. (Eds.M.Tsuchiya, et al.): "Mechanism of the passage of polymorphonuclear leukocytes between endothelial cells in hamster cheek pouch." Microcirculation annual. 9. 153-154 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Ohno, M.Katori, H.Hayashi, K.Nishiyama and K.Saigenji. (Eds.M.Tsuchiya, et al.): "A preventive mechanism of capsaisin in microcirculation against ethanol-induced gastric mucosal injury rat." Microcirculation annual. 9. 121-122 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Katori and M.Majima.: "Natriuretic role of the urinary kallikreinkinin system in the development of hypertension in rats." Asia Pacific J.Pharmacol. 8 (suppl.2). s20 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Hiramatsu, Y.Hayashi, S.Yamamoto, A.Hayashi, M.Sawada, N.Hamanaka and K.Yamashita.: "PGs LTs and essential fatty acids." (in press). (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Schweer, C.O.Meese, O.Furst et al.: Anal.Biochem.164. 156 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Kumlin, E.Granstrom.: Prostaglandins.32. 741 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] I.Sato, K.Kaji, I.Morita, M.Nagao and S.Murota.: "Augmentation of endothelin-1, prostacyclin and thromboxane A_2 secretion associated with in vitro ageing in cultured human umbilical vein endothelial cells." Mechanisms of Ageing and Development. 71. 73-84 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Sato, H.Seki and H.Sakamoto.: "Role of prostaglandins in pregnancy-induced hypertension." Ame.J.Kidney.Diseases. 17(2). 133-138 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Yokomizo, T.Izumi, T.Takahashi, T.Kasama, Y.Kobayashi, F.Sato, Y.Taketani and T.Shimizu.: "Enzymatic inactivation of leukotriene B4 by a novel enzyme found in the porcine kidney. Purfication and properities of leukotriene B4 12-hydroxydehydrogenase." J.Biol.Chem.268. 18128-18135 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] A.Honda, Y.Sugimoto, T.Namba, A.Watanabe, A.Irie, M.Negishi, S.Narumiya and A.Ichikawa.: "Cloning and expression of a cDNA for mouse prostaglandinE receptor EP_2 subtype." J.Biol.Chem.268(11). 7759-7762 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Narumiya, N.Hirata, T.Namba, Y.Hayashi, F.Ushikubi, Y.Sugimoto, M.Negishi and A.Ichikawa.: "Structure and function of prostanoid receptors." J.Lipid.Med.6. 155-161 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] A.Watanabe, Y.Sugimoto, A.Honda, A.Irie, T.Namba, M.Negishi, S.Ito, S.Narumiya and A.Ichikawa.: "Cloning and expression of cDNA for a mouse EP_1 subtype of prostaglandinE receptor." J.Biol.Chem.268(27). 20175-20178 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Namba, Y.Sugimoto, M.Negishi, A.Irie, F.Ushikubi, A.Kakizuka, S.Ito, A.Ichikawa and S.Narumiya.: "Alternative splicing of C-terminal tail of prostaglandinE receptor subtype EP3 determines G-protein specificity." Nature.365(6442). 166-170 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] R.M.Nusing, M.Hirata, A.Kakizuka, T.Eki, K.Ozawa and S.Narumiya.: "Characterization and chromosomal mapping of the human thromboxane A_2 receptor gene." J.Biol.Chem.268(33). 25253-25259 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] F.Ushikubi, Y.Aiba, K.Nakamura, T.Namba, M.Hirata, O.Mazda, Y.Katsura and S.Narumiya.: "Thromboxane A_2 receptor is highly expressed in mouse immature thymocytes and mediates DNA fragmentation and apoptosis." J.Exp.Med.178. 1825-1830 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] W.Takasaki, A.Nakagawa, F.Asai, S.Ushiyama, A.Sugidachi, K.Matsuda, T.Oshima and Y.Tanaka.: "Superiority of plasma 11-degydro-TXB_2 to TXB_2 as an index of in vivo TX formation in rabbits after dosing of CS-518, a TX synthase inhibitor." Thromb.Res.71(1). 69-76 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Uematsu, W.Takasaki, K.Kosuge, K.Wada, H.Matsuno, Y.Tanaka, N.Yamamura and M.Nakashima.: "Changes in plasma and urinary 11-dehydrothromboxane B_2 in healthy subjects produced by oral CS-518, a novel thromboxane synthase inhibitor." Eur.J.Clin.Pham.45. 283-286 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Omata, N.G.Abraham, B.Escalante and M.L.Schwartzman.: "Age-related changes in renal cytochrome P-450 arachidonic acid metabolism in spontaneously hypertensive rats." Am.J.Physiol.262. F8-F16 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Omata, N.G.Abraham and M.L.Schwartzman.: "Renal cytochrome P-450-arachidonic acid metabolism : localization and hormanal regulation in SHR." Am.J.Physiol.262. F591-F599 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Omata, E.Tsutsumi, H.L.Sheu, K.Yoshida, K.Yoshinaga and K.Abe.: "Role of renal cytochrome P450-dependent arachidonic acid (P-450-AA) metabolism in Dahl salt sensitive rats." J.Hypertens.10. S113 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Omata, N.G.Abraham and M.L.Schwartzman.: "Differential formations of renal cytochrome P450 dependent arachidonic acid metabolism in spontaneously hypertensive rats." J.Hypertens.10. S113 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Omata, K.Yoshinaga, K.Abe and M.L.Schwartzman.: "Effect of aging on renal cytochrome P450-dependent arachidonic acid metabolism in spontaneously hypertensive rats." Clin.Exp.Hyper.A14. 756 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Omata, E.Tsutsumi, H.L.Sheu, Y.Utsumi, N.Nushiro, T.Abe, S.Ito, N.Takahashi, S.Misawa, T.Yabe, M.Kohzuki, K.Tsunoda, Y.Imai and K.Abe.: "Role of renal cytochrome P450-arachidonate metabolites in hypertension of Dahl salt sensitive rats." Hyper.Res.15. 191 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Omata, K.Abe, H.L.Sheu, K.Yoshida, E.Tsutsumi, K.Yoshinaga, N.G.Abraham and M.L.Schwartzman.: "Roles of renal cytochrome P450-dependent arachidonic acid metabolites in hypertension." Tohoku J.Exp.Med.166. 93-106 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Omata, E.Tsutsumi, H.L.Sheu, Y.Utsumi and K.Abe.: "Effect of aging on renal cytochrome P450-dependent arachidonic acid metabolism in Dahl rats." J.Lipid.Mediators.6. 369-373 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] B.Escalante, K.Omata, W.Sessa, S.G.Lee, J.R.Falck and M.L.Schwartzman.: "20-hydroxyeicossatetraenoic acid is an endothelium-dependent vasoconstictor in rabbit arteries." Eur.J.Pharmacol.235. 1-7 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Takeuchi, T.Abe, N.Takahashi and K.Abe.: "Molecular cloning and intrarenal localization of rat prostaglandin E2 receptor EP3 subtype." Biochem.Biophys.Res.Commun.194. 885-891 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Takeuchi, T.Abe, N.Takahashi and K.Abe.: "Molecular cloning and internal localization of rat prostaglandin E2 receptor EP3 subtype." J.Amer.Soc.Nephrol.4. 501 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Takeuchi, T.Abe, N.Takahashi and K.Abe.: "Molecular cloning and intrarenal localization of rat prostaglandin E2 receptor EP3 subtype." Hypertension.22. 408 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Takeuchi, N.Takahashi, T.Abe and K.Abe.: "Two isoforms of the rat kidney EP3 receptor : Intrarenal expression and co-localization." Biochem.Biophys.Res.Commun.(in press). (1994)

    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 1995-03-27  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi