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(In Japanese)生体防御のメカニズム 異物排除システムの分子基盤

Research report code R990004239
Posted date Feb 6, 2001
  • (In Japanese)杉山 雄一
  • (In Japanese)東京大学大学院薬学系研究科
Research organization
  • (In Japanese)東京大学大学院薬学系研究科
Report name (In Japanese)生体防御のメカニズム 異物排除システムの分子基盤
Technology summary (In Japanese)生体は、細菌感染などに対しては免疫系を備えることにより防御を行っているが、医薬品を含む広範な低分子異物に対しては、分子変換および分子移送による排除という2つの防御機構を備えている。このうち、分子変換による排除に関する研究は最近開始されたに過ぎない。本研究では生態が備えている異物排除機構について、分子輸送による排除機構の解析、その分子変換による排除との関連、異物排除系の臓器相関と体内動態の解明とその制御という観点から検討を加えた。具体的には、
さらに最終的にこれらのプロセスを生理的薬物速度論に基づき、in vivoにおける低分子異物排除機構を統合的に解析した。
Research field
  • Cell physiology in general
  • Transport of cell membrane
  • Gene replication
  • Biological function
  • Biophylaxis and immune systems in general
Published papers related (In Japanese)(1)T. Hirohashi, H. Suzuki, K. Ito, K. Ogawa, K. Kume, T. Shimizu and Y.Sugiyama: Hepatic expression of multidrug resistance-associated protein(MRP)-like proteins maintained in Eisai hyperbilirubinemic rats(EHBR). Mol. Pharmacal. 53, 1068-1075 (1998)
(2)H.Kusuhara, H.Suzuki, M. Naito, T. Tsuruo and Y. Sugiyama: Characterization of efflux transport of organic anions in a mouse brain capillary endothelial cell line(MBED4). J. Pharmacol. Exp. Ther. 285, 1260-1265 (1998)
(3)T. Yamada, Y. Kato, H. Kusuhara, M. Lemaire, and Y.Sugiyama: Characterization of the transporter of a cationic octapeptide, octreotide, in rat bile canalicular membrane: Possible involvement of P-glycoprotein. Biol. Pharm. Bull. 21(8) 874-878 (1998)
(4)H. Kusuhara. Y.-H. Han, M. Shimoda, E. Kokue, H. Suzuki and Y. Sugiyama: Reduced folate derivatives are endogenous substrates for cMOAT in rats. Am. J. Physiol. 275, G789-G796 (1998)
(5)Y. Kato, S. Akhteruzzaman, A. Hisaka, and Y. Sugiyama:Hepatobiliary transport governs the overall elimination of peptidic endothelin antagonists in rats. J. Pharmacol. Exp. Ther. 288, 568-574 (1999)
(6)X. Chu, Y. Kato, K. Ueda, H. Suzuki, K. Niinuma, C.A. Tyson, V. Weizer, J.E. Dabbs, R. Froelich, C.E. Green, and Y. Sugiyam:Biliary excretion mechanism of CPT-11 and its metabolites in humans: Involvement of primary active transporters. Cancer Res. 58, 5137-5743 (1998)
(7)S. Akhteruzzaman, Y. Kato, A. Hisaka, and Y. Sugiyama:Primary active transport of peptidic endothelin antagonists on bile canalicular membrane in rats. J. Pharmacol. Exp. Ther. 288, 575-581 (1999)
(8)H.Kouzuki, H.Suzuki, K.Ito, R. Ohashi and Y.Sugiyama:Contribution of sodium taurocholate co-transporting polypeptide to the uptake of Ligands into rat hepatocytes. J. Pharmacol. Exp. Ther. 286, 1043-1050 (1998)
(9)H.Ishizuka, K.Konno, H.Naganuma, K.Nishimura, H.Kouzuki, H.Suzuki, B.Stieger, P.J.Meier and Y.Sugiyma:Transport of temocaprilat into rat hepatocytes: Role of organic anion transportin gpolypeptide (oatp1). J. Pharmacol. Exp. Ther..287, 37-42(1998)
(10)Y.Kiuchi, H.Suzuki, T.Hirohashi, C.A.Tyson and Y.Sugiyama:cDNA cloning and inducible expression of human multidrug resistance associated protein 3(MRP3). FEBS Lett. 433, 149-152 (1998)
(11)H.Kouzuki, H.Suzuki, R.Ohashi, K.Ito and Y.Sugiyama:Contribution of organic anion transporting polypeptide to the uptake of its possible substrates into rat hepatocytes. J. Pharmacol. Exp. Ther. 288, 627-634 (1999)
(12)S.Kinoshita, H.Suzuki, K.Ito, K.Kume, T.Shimizu and Y.Sugiyama: Transfected rat cMOAT is functionally expressed on the apical membrane in Madin-Darby canine kidney(MDCK)cells. Pharm. Res. 15(12),1851-1856(1999)
(13)X.-Y.Chu, H.Suzuki, K.Ueda, Y.Kato, S.Akiyama and Y.Sugiyama:Active efflux of CPT-11 and its metabolites in human KB-derived cell lines. J. Pharmacol. Exp. Ther. 288, 735-741 (1999)
(14)M.Honma, H.Suzuki, H.Kusuhara, M.Naito, T.Tsuruo and Y.Sugiyama: High affinity efflux transport system for glutathione conjugates on the luminal membrane of a mouse brain capillary endothelial cell line(MBEC4). J. Pharmacol. Exp. Ther. 288, 198-203 (1999)
(15)S.H.Song, H.Suzuki, T.Terasaki, M.Lemaire and Y.Sugiyama:Modulation of the tumor disposition of vinca alkaloids by PSC 833 in vitro and in vivo. J. Pharmacol. Exp. Ther..287,963-968(1998)
(16)H.Kusuhara, H.Suzuki and Y.Sugiyama: The role of P-glycoprotein and canalicular multispecific organic anion transporter(cMOAT) in the hepatobiliary excretion of drugs. J. Pharm. Sci. 87, 0125-1040 (1998)
Research project
  • Core Research for Evolutional Science and Technology;Host Defense Mechanism
Information research report
  • (In Japanese)杉山 雄一. 生体防御のメカニズム 異物排除システムの分子基盤. 戦略的基礎研究推進事業 平成10年度 研究年報,1999. p.206 - 210.