1996 Fiscal Year Annual Research Report

薬物の臓器特異的移行機構の解明とその薬効・動態制御への応用

Research Project

Project/Area Number	07307035
Research Institution	Kanazawa University
Principal Investigator	辻彰金沢大学, 薬学部, 教授 (10019664)
Co-Investigator(Kenkyū-buntansha)	真弓忠範大阪大学, 薬学部, 教授 (00098485) 橋田充京都大学, 薬学部, 教授 (20135594) 杉山雄一東京大学, 薬学部, 教授 (80090471) 粟津荘司東京薬科大学, 薬学部, 教授 (60012621) 花野学日本大学, 薬学部, 教授 (60012598)
Keywords	drug delivery / transporter / receptor / efflux pump / tissue targeting / pharmacokinetics / blood-brain barrier / cloning
Research Abstract	本研究においては、薬物動態と薬効・毒性発現に影響するトランスポータ、レセプター、臓器・細胞特異的な糖質・蛋白質など諸因子について総合的に解析し、合理的な薬物動態及び薬効制御法の開発を目指した。本年度では、次に示す結果を得た。 1.薬物の消化管からの吸収・分泌、肝・腎排泄、脳などの臓器分布・排出に関与するトランスポータ(TP)群の存在の示唆及びそれらの化学構造認識・輸送特性の解明、_cMOAT,OAT-K1,OCT2などのTP群のクローニングとその機能解析、及びこれらのTP群の組織分布性を明らかとした。また、吸着介在エンドサイトーシスによってペプチドを脳に送達する道を開いた(辻、杉山、乾、玉井)。口腟における薬物動態に関し、ヒト口腟粘膜還流セルを用いて受動輸送と特殊輸送において部位間差があることを明らかにした(木村)。 2.グリコシド化、粘膜接着性、イオントフォレ-シスの利用あるいは細胞間隙拡大物質による低・高分子薬物の消化管吸収促進機構を解明した(粟津、林)。 3.分画ヘパリンの血漿蛋白質が介在する肝移行制御(渡辺)、糖鎖認識機構に基づいたレセプター介在性エンドサイトーシスを利用した肝細胞内選択的送達法を確立した(橋田)。虚血性心脳血管障害などの各種疾患に活性酸素やNOラジカルが病態制御因子として重要な役割を演じていることをつきとめた(井上)。また、腫瘍臓器血管内皮細胞に対するモノクロナール抗体を利用した斬新な癌ミサイル療法の道を開いた(真弓)。 4.ヒト_<α1>受容体のクローニングとその細胞内情報伝達機構を解析した(辻本)。また、脳内および抹消組織には、それぞれN^3フェナシルウリジンおよびウリジンと強い親和性を有するレセプターの存在を示唆する新規な結果を得た(山本)。中枢性鎮痛薬の血漿中・脳内濃度と鎮痛効果の時間推移を薬物動態学的に解析し、神経活動の制御機構を解明する方法を開発した(花野)。

Research Products
(121 results)

All Other

All Publications (121 results)

[Publications] T.Ohnishi: "In vivo and vitro evidence for ATP-dependency of P-glycoprotein-mediated efflux of doxorubicin at the blood-brain barrier" Biochem. Pharmacol.49. 1541-1544 (1995)
[Publications] I.Tamai: "Na^+ and Cl^- -dependent transport of taurine at the blood-brain barrier" Biochem. Pharmacol.50. 1783-1793 (1995)
[Publications] H.Takanaga: "cDNA cloning and functional characterization of rat intestinal monocarboxylate transporter" Biochem. Biophys. Res.Commun.217. 370-377 (1995)
[Publications] T.Terasaki: "Hepatic uptake of octeotide,a long-acting somatostatin analogue,via a bile acid transport system" Pharm. Res.12. 12-17 (1995)
[Publications] I.Tamai: "Functional expression of transporter for β-lactam antibiotics and dipeptides in Xenopus laevis oocytes injected with messenger RNA from human,rat and rabbit small intestines" J.Pharmacol. Exp.Ther.273. 26-31 (1995)
[Publications] T.Minagawa: "Species differences in hydrolysis of isocarbacyclin methyl ester (TEI9090) by blood esterases" Biochem. Pharmacol.49. 1361-1366 (1995)
[Publications] I.Tamai: "Participation of a proton-cotransporter,MCTI,in the intestinal transport of monocarboxylic acids" Biochem. Biophys. Res.Commun.214. 482-489 (1995)
[Publications] I.Tamai: "Proton-cotransport of pravastatin across intestinal brush-border membrane" Pharm. Res.12. 1727-1732 (1995)
[Publications] 玉井郁巳: "ジペプチドトランスポーターと医薬品の消化管吸収" ファルマシア. 31. 493-497 (1995)
[Publications] 辻彰: "薬物相互作用-P糖蛋白質" ファルマシア. 31. 997-1001 (1995)
[Publications] S.Matsumoto: "Transport characteristics of ceftibuten,a new cephalosporin antibiotic,via the apical H^+/dipeptide cotransport system in the human intestinal cell line C_<aco>-2 : Regulation by cell growth." Pharm. Res.12(10). 1483-1487 (1995)
[Publications] M.Hirai: "Cepharanthin,a multidrug resistant modifier,is a substrate for P-glycoprotein" J.Pharmacol. Exp.Ther.275(1). 73-78 (1995)
[Publications] Y.Tomita: "Transport of oral cephalosporins by the H^+/dipeptide cotransporter and distribution of the transport activity in isolated rabbit intestinal epithelial cells" J.Pharmacol. Exp.Ther.272(1). 63-69 (1995)
[Publications] J.Nagai: "Specificity of p-aminohippurate transport system in the OK kidney epithelial cell line" J.Pharmacol. Exp.Ther.274(3). 1161-1166 (1995)
[Publications] H.Saito: "Cloning and characterization of a rat H^+/peptide cotransporter mediating absorption of β-lactam antibiotics in the intestine and kidney" J.Pharmacol. Exp.Ther.275(3). 1631-1637 (1995)
[Publications] K.Iwata: "High-performance liquid chromatographic determination of diadenosine 5^|,5^<|||>-p1,p4-tetraphosphate with precolumn fluorescence derivatization and its application to metabolism study in whole blood" J.Chromatogr. B.667(2). 339-343 (1995)
[Publications] K.Iwata: "Ca^<2+> Dependency of diadenosine 5^|,5^<|||>-p1,p4-tetraphosphate degradation in dog plasma" Biol. Pharm. Bull.18(5). 788-790 (1995)
[Publications] T.Nakagawa: "Biopharmaceutical studies on drug/conjugated-metabolite interactions. I.Fate of acetaminophen sulfate,a major conjugated metabolite of acetaminophen,in rats" Int.J.Pharm.121(1). 55-63 (1995)
[Publications] Z.Wang: "Gastrointestinal absorption characteristics of glycyrrhizin from glycyrrhiza extract" Biol. Pharm. Bull.18(9). 1238-1241 (1995)
[Publications] T.Kimura: "Disposition of diadenosine 5^|,5^<|||>-P1,P4-tetraphosphate (Ap4A) in rats" Biol. Pharm. Bull.18(11). 1556-1559 (1995)
[Publications] T.Kimura: "プロドラッグによるAzidothymidineの脳移行性改善" DDS. 10(6). 413-417 (1995)
[Publications] M.Nishikawa: "Galactosylated proteins are recognized by the liver according to the surface density of galactose moieties" Am.J.Physiol.268(5). G849-G856 (1995)
[Publications] M.Nishikawa: "Desigh for cell-specific targeting of proteins utilizing sugar-recognition mechanism : effect of molecular weight of proteins on targeting efficiency" Pharm. Res.12(2). 209-214 (1995)
[Publications] M.Hashida: "Hepatic targeting of drugs and proteins by chemical modification" J.Controll. Release. 36(1-2). 99-107 (1995)
[Publications] M.Motoya: "糖鎖認識機構を利用した細胞特異的薬物ターゲティング(Cell-specific targeting of drugs utilizing sugar-recognition systems)" Pharm. Tech. Japan. 11(4). 395-403 (1995)
[Publications] M.Tomita: "Absorption-enhancing mechanism of sodium caprate and decanoylcarnitine in Caco-2 cells" J.Pharmacol. Exp.Ther.272(2). 739-743 (1995)
[Publications] T.Kimura: "Localization of uridine receptor on synaptic membranes" Sleep Res.24A. 128 (1995)
[Publications] T.Kimura: "Binding affinity of N^3-substituted uridine for synaptic membrane and their CNS depressant effects" Nucleic Acids Symposium Series. 34. 147-148 (1995)
[Publications] M.Haba: "Uptake mechanism of fractionated ^3H-heparin by isolated rat kupffer cells" Xenobio. Metabol. Dispos.10(suppl. s104-107 (1995)
[Publications] 掛江敦之: "血液脳関門-静的障壁からダイナミック・インターフェースへ-脳へのドラッグデリバリーの最近の進歩-その4-" Pharm. Tech. Japan. 11. 23-25 (1995)
[Publications] M.Tomita: "Absorption-enhancing mechanism of sodium caprate and decanoylcarnitine inCaco-2cells" J.Pharmcol. Exp. Ther.272. 739-743 (1995)
[Publications] Y.Takehara: "Oxygen dependent regulation of mitochondrial functions by nitric oxide" Arch. Biochem. Biophys.323(1). 27-32 (1995)
[Publications] I.Matsuoka: "Impact of erythrocytes on mouse embryonal develoment in vitro" FEBS Lett.371. 297-299 (1995)
[Publications] Z.Radak: "Superoxide dismutase derivative prevents the exhaustive exercise induced oxidative damage in liver and kidney of rats" J.Applied Physiol.79. 129-135 (1995)
[Publications] S.Kawamoto: "Changes in the circulatory status and transport functions of the liver induced by reactive oxygen species." Am.J.Physiol.268. G47-G53 (1995)
[Publications] Y.Nishimura: "Inhibition of puromycin-inducedrenal injury by a superoxide dismutase with prolonged half-life in the circulation" Nephron. 70. 460-465 (1995)
[Publications] K.Ono: "A negative chronotropic effect of endothelin-1 mediated through ETA receptor in guinea pig atria" Circ.Res.76. 284-292 (1995)
[Publications] T.Kuwabara: "Receptor-mediated clearnance of G-CSF derivative nartograstim in bone marrow of rats" Am.J.Physiol.269. E1-E9 (1995)
[Publications] T.Kuwabara: "Saturable uptake of a recombinant human granulocyte colony stimulating factor derivative nartograstim by the bone marrow and spleen of rats in vivo" J.Pharmacol. Exp.Ther.273. 1114-1122 (1995)
[Publications] H.Takikawa: "Binding of lithocholate and its glucuronide and sulfate by human serum albumin" Biochem. Biophys. Acta. 1244. 277-282 (1995)
[Publications] Ke-Xin.Liu: "Change in hepatic handling of hepatocyte growth factor during liver regeneration in rats" Am.J.Physiol.269. G1-G9 (1995)
[Publications] A.Hirasawa: "Cloning,functional expression and tissue distribution of human α 1c-adrenoceptor splice variants" FEBS Lett.363. 256-260 (1995)
[Publications] T.A.Esbenshade: "Cloning of the human α 1A/D-adrenergic receptor and inducible expression of three human subtypes in SKNMC cells" Mol.Pharmacol.47. 977-985 (1995)
[Publications] K.Horie: "Selectivity of the imidazoline α-adrenoceptor agonists (oxymetazoline and cirazoline) for human cloned α 1-adrenoceptor subtypes" Brit.J.Pharmacol.116. 1611-1618 (1995)
[Publications] K.Shibata: "KMD-3213,a novel,potent α la-adrenoceptor-selective antagonist : Characterization using recombinant human α 1-adrenoceptors and native tissues" Mol.Pharmacol.48. 250-258 (1995)
[Publications] N.Utoguchi: "Effect of tumor cell-conditioned medium on endothelial macromolecular permeability and its correlation with collagen" Brit.J.Cancer. 73(1). 24-28 (1996)
[Publications] H.Mizuguchi: "Glial conditioned medium elevates alkaline phosphatase activity in cultured bovine aortic endothelial cells" Microvasular Res.50. 129-132 (1995)
[Publications] Y.Tsutsumi: "Molecular design of hybrid tumor necrosis factor-α with polyethylene glycol increases its anti-tumor potency" Brit.J.Cancer. 71. 963-968 (1995)
[Publications] N.Utoguchi: "Isolation and properties of tumor-derived endothelial cells from rat KMT-17 fibrosarcoma" Jpn.J.Cancer Res.86. 193-201 (1995)
[Publications] N.Utoguchi: "Tumor-conditioned medium increases macromolecular permeability of endothelial cell monolayer" Cancer Lett.89. 7-14 (1995)
[Publications] T.Kimura: "Central nervous system depressant effects of N^3-substituted derivatives of deoxyuridine in mice" Biol. Pharm. Bull.19(1). 142-145 (1996)
[Publications] T.Kimura: "Localization of uridine receptor on synaptic membranes" Sleep Res.24A. 128 (1995)
[Publications] J.Watanabe: "Uptake of fractionated ^3 H-heparin by isolated rat Kupffer cells" Pharm.Res.12. 1092-1095 (1995)
[Publications] J.Watanabe: "Uptake of low molecular weight fractionated 〔^3H〕 heparin by rat hepatocytes in the primary culture" Biol. Pharm. Bull.18. 443-446 (1995)
[Publications] Y.Sai: "Immunolocarization and pharmacological relevance of oligopeptide transporter PepT1 in intestinal absorption of β-lactam antibiotics" FEBS Lett.392(1). 25-29 (1996)
[Publications] J.Komura: "Na^+ and Cl^- dependent transport of β-alanine across the blood-brain barrier" J.Neurochem.67(1). 330-305 (1996)
[Publications] K.Miyamoto: "Sequence,tissue distribution and developmental changes in rat intestinal oligopeptide transporter" Biochim. Biophys. Acta. 1305(1). 34-38 (1996)
[Publications] A.Tsuji: "Carrier-mediated intestinal transport of drugs" Pharm.Res.13(7). 963-977 (1996)
[Publications] I.Tamai: "Carrier-mediated approaches for oral drug delivery" Adv.Drug Delivery Rev.20. 5-32 (1996)
[Publications] I.Tamai: "Drug delivery through the blood-brain barrier" Adv.Drug Delivery Rev.19. 401-424 (1996)
[Publications] T.Ogihara: "Stereoselective and carrier-mediated transport of monocarboxylic acids across Caco-2 cells" Pharm.Res.13(12). 1828-1832 (1996)
[Publications] T.Terao: "Active secretion of drugs from the small intestinal epithelium in rats by P-glycoprotein functioning as as absorption barrier" J.Pharm. Pharmacol.48. 1083-1089 (1996)
[Publications] T.Minagawa: "Blood-brain-barrier transport of lipid microspheres containing clinoprost,a prostaglandin I2 analogue" J.Pharm. Pharmacol.48. 1016-1022 (1996)
[Publications] M.Tomita: "Absorption-enhancing mechanism of EDTA,caprate,and decanyolcarnitine in Caco-2 cells" J.Pharm. Sci.85(6). 608-611 (1996)
[Publications] T.Ohtomo: "Transport of levofloxacin in a kidney epithelial cell line,LLC-PK 1: Interaction with organic cation transporters in apical and basolateral membranes" J.Pharmacol. Exp.Ther.276(3). 1143-1148 (1996)
[Publications] H.Ogihara: "Immuno-localization of N^+/peptide cotransporter in rat digestive tract" Biochem. Biophys. Res.Commun.220(3). 848-852 (1996)
[Publications] H.Saito: "Molecular cloning and tissue distribution of rat peptide transporter PEPT2" Biochim. Biophys. Acta. 1280(2). 173-177 (1996)
[Publications] K.Tanaka: "Effect of cyclosporin analogues and FK506 on transcellular transport of daunorubicin and vinblastine via P-glycoprotein" Pharm.Res.13(7). 1073-1077 (1996)
[Publications] T.Nabekura: "Modulation of organic cation transport and lipid fluidity by benzyl alcohol in rat renal brush-border membranes" Pharm.Res.13(7). 1069-1072 (1996)
[Publications] M.Okuda: "cDNA cloning and functional expression of a novel rat kidney organic cation transporter,OCT2" Biochem. Biophys. Res.Commun.224(2). 500-507 (1996)
[Publications] H.Saito: "Cloning and functional characterization of a novel rat organic anion transporter mediating basolateral uptake of methotrexate in the kidney" J.Biol.Chem.271(34). 20719-20725 (1996)
[Publications] M.Takano: "Regulation of p-aminohippurate transport by protein kinase C in OK kidney epithelial cells" Am.J.Physiol.271(2). F469-F475 (1996)
[Publications] T.Nabekura: "Cholesterol modulates organic cation transport activity and lipid fluidity in rat renal brush-border membranes" Biochim. Biophys. Acta. 1283(2). 232-236 (1996)
[Publications] T.Terada: "Identification of the histidine residues involved in substrate recognition by rat H^+/peptide cotransporter. PEPT1" FEBS Lett.394(2). 196-200 (1996)
[Publications] H.Saito: "Na^+-Dependent uptake of 1,5-anhydro-D-glucitol via the transport systems for D-glucose and D-mannose in kidnev epithelial cell line. LLC-PK1" Jpn.J.Nephrology.38(10). 435-440 (1996)
[Publications] M.Nishikawa: "Oxygen-Dependent Regulation of Ascites Tumor Cell Respiration by Nitric Oxide" Cancer Res.56. 4535-4540 (1996)
[Publications] Y.Minamiyama: "Albumin is an important vascular tonus regulator as a reservoir of nitric oxide" Biochem. Biophys. Res.Commun.225. 112-11 (1996)
[Publications] M.Kashiba: "Role of ascorbic acid in the metabolism of S-nitrosoglutathione" FEBS Lett.389. 149-152 (1996)
[Publications] Y.Fujino: "DNA fragmentation of oocytes in aged mice." Human Reproduction. 11. 1480-1483 (1996)
[Publications] Y.Inai: "Oxygen-dependent regulation of Ehrlich ascites tumor cell respiration by NO" Cell Struct. Funct.21. 151-157 (1996)
[Publications] S.Kashiwagi: "Characterization of two distinct potassium channels and gap junctional communication in cultured rat hepatic stellate cells" Am.J.Physiol.(in press). (1996)
[Publications] Y.Minamiyama: "Dynamic Aspects of glutathione and nitric oxide metabolism in endotoxemic rats" Am.J.Physiol.34. G575-581 (1996)
[Publications] Y.Takehara: "Molecular Mechanism for NO-dependent regulation of mitochondrial energy transduction" Free Radical Biol.& Medicine. (in press). (1996)
[Publications] Y.Takehara: "Proposed mechanism for the reversible inhibition of mitochondrial respiration by nitric oxide" Cell Strnct. Funct. 21. 251-258 (1996)
[Publications] H.Hanada: "Does reactive oxygen underlie the mechanism for the apoptotic disappearance of tadpole tail" Free Radical Boil.& Medicine. (in press). (1996)
[Publications] M.Yabuki: "Oxygen-dependent fragmentation of cellular DNA by nitric oxide" Free Rad.Res.Commun.(in press). (1996)
[Publications] S.Iha: "Oxygen-dependent inhibition of neutrophil respiratory burst by nitric oxide" Free Radical Res.Commun.(in press). (1996)
[Publications] N.Kawada: "Effect of endothelins on hepatic stellate cells" Hepatology. (in press). (1996)
[Publications] M.Yabuki: "Enhanced DNA fragmentation in HL-60 cells by nitric oxide under low oxygen tension" Free Rad.Res.(in press). (1996)
[Publications] S.Okada: "Nitric oxide,a physiological modulator of mitochondrial function" Physiol.Chem.Physics. 28. 69-82 (1996)
[Publications] I.Matsuoka: "Impact of erythrocytes on mouse embryonal" FEBS Lett.371. 297-299 (1996)
[Publications] Y.Fujino: "DNA fragmentation of oocytes in aged mice" Human Reproduction. 11. 1480-1483 (1996)
[Publications] N.Kawada: "Expression of heat shock protein 47 in mouse liver" Cell Tissue Res.284. 341-346 (1996)
[Publications] N.Kawada: "Inhibition of myofibroblastic transformation of rat hepatic stellete cells by methylxanthine and cAMP" Dig.Dis.Sci.41. 1022-1029 (1996)
[Publications] N.Kawada: "Pathophysiology of acute obstructive cholangitis" J.hep.Bil.pancr.Surg.3. 4-8 (1996)
[Publications] T.Sawamoto: "Pharmacokinetics of acetaminophen sulfate after oral administration in rats : analysis of plasma profiles exhibiting non-linear second peak" Biol.Pharm.Bull.19(1). 77-82 (1996)
[Publications] K.Iwata: "Disposition of intravenously administered adenosine 5^|-phosphosulfate (APS) in rats" Biol. Pharm. Bull.19(3). 438-443 (1996)
[Publications] T.Kimura: "Oral administration of insulin as poly (vinyl alcohol)-gel spheres in diabetic rats" Biol. Pharm. Bull.19(6). 897-900 (1996)
[Publications] Z.Wang: "Pharmacokinetics of glycyrrhizin in rats with D-galactosamine-induced hepatic disease" Biol. Pharm. Bull.19(6). 901-904 (1996)
[Publications] A.Tsuji: "Peptide Based Drug Design : Controlling Transport and Metabolism" American Chemical Society, 34 (1995)
[Publications] T.Terasaki: "Peptide-based drug design : Controlling Transport and Metabolism" American Chemical Society, 20 (1995)
[Publications] 乾賢一: "腎臓学-病態生理からのアプローチ" 南江堂, 442 (1995)
[Publications] M.Inoue: "Brain Physiology and Disorder" Academic Press, 8 (1996)
[Publications] M.Inoue: "Biology of nitric oxide" Portland Press (in press), (1996)
[Publications] Y.Minamiyama: "Biology of nitric oxide" Portland Press (in press), (1996)
[Publications] S.Takemura: "Biology of nitric oxide" Portland Press (in press), (1996)
[Publications] M.Inoue: "Food and Free Radicals" Plenum Press (in press), (1996)
[Publications] M.Inoue: "Meth.Enzymol.Vol.269" Academic Press, 6 (1996)
[Publications] M.Inoue: "Meth.Enzymol.Vol.268" Academic Press, 7 (1996)
[Publications] N.Kawada: "Cells of the Hepatic Sinusoid Vol.6" (in press), (1996)
[Publications] M.Inoue: "Cells of the Hepatic Sinusoid Vol.6" (in press), (1996)
[Publications] 井上正康: "活性酸素と医食同源" 共立出版, 356 (1996)
[Publications] 井上正康: "活性酸素とシグナル伝達" 講談社, 220 (1996)
[Publications] 井上正康: "アポトーシスの分子機構と病態" メディカルトリビューン社, 126 (1996)
[Publications] Y.Sugiyama: "Advanced Biomaterials in Biomedical Engineering and Drug Delivery Systems." Springer-Verlag, 6 (1996)
[Publications] N.Okudaira: "Model Systems Used for Biopharmaceutical Assessment of Drug Absorption and Metabolism Vol.12" 28 (1996)
[Publications] 杉山雄一: "薬理学(上)" 廣川書店, 47 (1996)
[Publications] 楠原洋之: "P糖蛋白質の生理機能" 中外医学社, 7 (1996)
[Publications] G.Tsujimoto: "Receptor desensitization and Ca^<2+>-signaling : Cellular aspects of possible molecular dynamics" Japan Scientific Societies Press, 22 (1996)
[Publications] 辻本豪三: "薬の正しい使い方(日本医師会生涯教育シリーズ)" 医学書院, 3 (1996)
[Publications] 井上昌次郎: "睡眠のメカニズム" 朝倉書店, (1997)

1996 Fiscal Year Annual Research Report

薬物の臓器特異的移行機構の解明とその薬効・動態制御への応用

Principal Investigator

辻 彰 金沢大学, 薬学部, 教授 (10019664)

Research Products

[Publications] T.Ohnishi: "In vivo and vitro evidence for ATP-dependency of P-glycoprotein-mediated efflux of doxorubicin at the blood-brain barrier" Biochem. Pharmacol.49. 1541-1544 (1995)

[Publications] I.Tamai: "Na^+ and Cl^- -dependent transport of taurine at the blood-brain barrier" Biochem. Pharmacol.50. 1783-1793 (1995)

[Publications] H.Takanaga: "cDNA cloning and functional characterization of rat intestinal monocarboxylate transporter" Biochem. Biophys. Res.Commun.217. 370-377 (1995)

[Publications] T.Terasaki: "Hepatic uptake of octeotide,a long-acting somatostatin analogue,via a bile acid transport system" Pharm. Res.12. 12-17 (1995)

[Publications] I.Tamai: "Functional expression of transporter for β-lactam antibiotics and dipeptides in Xenopus laevis oocytes injected with messenger RNA from human,rat and rabbit small intestines" J.Pharmacol. Exp.Ther.273. 26-31 (1995)

[Publications] T.Minagawa: "Species differences in hydrolysis of isocarbacyclin methyl ester (TEI9090) by blood esterases" Biochem. Pharmacol.49. 1361-1366 (1995)

[Publications] I.Tamai: "Participation of a proton-cotransporter,MCTI,in the intestinal transport of monocarboxylic acids" Biochem. Biophys. Res.Commun.214. 482-489 (1995)

[Publications] I.Tamai: "Proton-cotransport of pravastatin across intestinal brush-border membrane" Pharm. Res.12. 1727-1732 (1995)

[Publications] 玉井郁巳: "ジペプチドトランスポーターと医薬品の消化管吸収" ファルマシア. 31. 493-497 (1995)

[Publications] 辻 彰: "薬物相互作用-P糖蛋白質" ファルマシア. 31. 997-1001 (1995)

[Publications] S.Matsumoto: "Transport characteristics of ceftibuten,a new cephalosporin antibiotic,via the apical H^+/dipeptide cotransport system in the human intestinal cell line C_<aco>-2 : Regulation by cell growth." Pharm. Res.12(10). 1483-1487 (1995)

[Publications] M.Hirai: "Cepharanthin,a multidrug resistant modifier,is a substrate for P-glycoprotein" J.Pharmacol. Exp.Ther.275(1). 73-78 (1995)

[Publications] Y.Tomita: "Transport of oral cephalosporins by the H^+/dipeptide cotransporter and distribution of the transport activity in isolated rabbit intestinal epithelial cells" J.Pharmacol. Exp.Ther.272(1). 63-69 (1995)

[Publications] J.Nagai: "Specificity of p-aminohippurate transport system in the OK kidney epithelial cell line" J.Pharmacol. Exp.Ther.274(3). 1161-1166 (1995)

[Publications] H.Saito: "Cloning and characterization of a rat H^+/peptide cotransporter mediating absorption of β-lactam antibiotics in the intestine and kidney" J.Pharmacol. Exp.Ther.275(3). 1631-1637 (1995)

[Publications] K.Iwata: "High-performance liquid chromatographic determination of diadenosine 5^|,5^<|||>-p1,p4-tetraphosphate with precolumn fluorescence derivatization and its application to metabolism study in whole blood" J.Chromatogr. B.667(2). 339-343 (1995)

[Publications] K.Iwata: "Ca^<2+> Dependency of diadenosine 5^|,5^<|||>-p1,p4-tetraphosphate degradation in dog plasma" Biol. Pharm. Bull.18(5). 788-790 (1995)

[Publications] T.Nakagawa: "Biopharmaceutical studies on drug/conjugated-metabolite interactions. I.Fate of acetaminophen sulfate,a major conjugated metabolite of acetaminophen,in rats" Int.J.Pharm.121(1). 55-63 (1995)

[Publications] Z.Wang: "Gastrointestinal absorption characteristics of glycyrrhizin from glycyrrhiza extract" Biol. Pharm. Bull.18(9). 1238-1241 (1995)

[Publications] T.Kimura: "Disposition of diadenosine 5^|,5^<|||>-P1,P4-tetraphosphate (Ap4A) in rats" Biol. Pharm. Bull.18(11). 1556-1559 (1995)

[Publications] T.Kimura: "プロドラッグによるAzidothymidineの脳移行性改善" DDS. 10(6). 413-417 (1995)

[Publications] M.Nishikawa: "Galactosylated proteins are recognized by the liver according to the surface density of galactose moieties" Am.J.Physiol.268(5). G849-G856 (1995)

[Publications] M.Nishikawa: "Desigh for cell-specific targeting of proteins utilizing sugar-recognition mechanism : effect of molecular weight of proteins on targeting efficiency" Pharm. Res.12(2). 209-214 (1995)

[Publications] M.Hashida: "Hepatic targeting of drugs and proteins by chemical modification" J.Controll. Release. 36(1-2). 99-107 (1995)

[Publications] M.Motoya: "糖鎖認識機構を利用した細胞特異的薬物ターゲティング(Cell-specific targeting of drugs utilizing sugar-recognition systems)" Pharm. Tech. Japan. 11(4). 395-403 (1995)

[Publications] M.Tomita: "Absorption-enhancing mechanism of sodium caprate and decanoylcarnitine in Caco-2 cells" J.Pharmacol. Exp.Ther.272(2). 739-743 (1995)

[Publications] T.Kimura: "Localization of uridine receptor on synaptic membranes" Sleep Res.24A. 128 (1995)

[Publications] T.Kimura: "Binding affinity of N^3-substituted uridine for synaptic membrane and their CNS depressant effects" Nucleic Acids Symposium Series. 34. 147-148 (1995)

[Publications] M.Haba: "Uptake mechanism of fractionated ^3H-heparin by isolated rat kupffer cells" Xenobio. Metabol. Dispos.10(suppl. s104-107 (1995)

[Publications] 掛江敦之: "血液脳関門-静的障壁からダイナミック・インターフェースへ-脳へのドラッグデリバリーの最近の進歩-その4-" Pharm. Tech. Japan. 11. 23-25 (1995)

[Publications] M.Tomita: "Absorption-enhancing mechanism of sodium caprate and decanoylcarnitine inCaco-2cells" J.Pharmcol. Exp. Ther.272. 739-743 (1995)

[Publications] Y.Takehara: "Oxygen dependent regulation of mitochondrial functions by nitric oxide" Arch. Biochem. Biophys.323(1). 27-32 (1995)

[Publications] I.Matsuoka: "Impact of erythrocytes on mouse embryonal develoment in vitro" FEBS Lett.371. 297-299 (1995)

[Publications] Z.Radak: "Superoxide dismutase derivative prevents the exhaustive exercise induced oxidative damage in liver and kidney of rats" J.Applied Physiol.79. 129-135 (1995)

[Publications] S.Kawamoto: "Changes in the circulatory status and transport functions of the liver induced by reactive oxygen species." Am.J.Physiol.268. G47-G53 (1995)

[Publications] Y.Nishimura: "Inhibition of puromycin-inducedrenal injury by a superoxide dismutase with prolonged half-life in the circulation" Nephron. 70. 460-465 (1995)

[Publications] K.Ono: "A negative chronotropic effect of endothelin-1 mediated through ETA receptor in guinea pig atria" Circ.Res.76. 284-292 (1995)

[Publications] T.Kuwabara: "Receptor-mediated clearnance of G-CSF derivative nartograstim in bone marrow of rats" Am.J.Physiol.269. E1-E9 (1995)

[Publications] T.Kuwabara: "Saturable uptake of a recombinant human granulocyte colony stimulating factor derivative nartograstim by the bone marrow and spleen of rats in vivo" J.Pharmacol. Exp.Ther.273. 1114-1122 (1995)

[Publications] H.Takikawa: "Binding of lithocholate and its glucuronide and sulfate by human serum albumin" Biochem. Biophys. Acta. 1244. 277-282 (1995)

[Publications] Ke-Xin.Liu: "Change in hepatic handling of hepatocyte growth factor during liver regeneration in rats" Am.J.Physiol.269. G1-G9 (1995)

[Publications] A.Hirasawa: "Cloning,functional expression and tissue distribution of human α 1c-adrenoceptor splice variants" FEBS Lett.363. 256-260 (1995)

[Publications] T.A.Esbenshade: "Cloning of the human α 1A/D-adrenergic receptor and inducible expression of three human subtypes in SKNMC cells" Mol.Pharmacol.47. 977-985 (1995)

[Publications] K.Horie: "Selectivity of the imidazoline α-adrenoceptor agonists (oxymetazoline and cirazoline) for human cloned α 1-adrenoceptor subtypes" Brit.J.Pharmacol.116. 1611-1618 (1995)

[Publications] K.Shibata: "KMD-3213,a novel,potent α la-adrenoceptor-selective antagonist : Characterization using recombinant human α 1-adrenoceptors and native tissues" Mol.Pharmacol.48. 250-258 (1995)

[Publications] N.Utoguchi: "Effect of tumor cell-conditioned medium on endothelial macromolecular permeability and its correlation with collagen" Brit.J.Cancer. 73(1). 24-28 (1996)

[Publications] H.Mizuguchi: "Glial conditioned medium elevates alkaline phosphatase activity in cultured bovine aortic endothelial cells" Microvasular Res.50. 129-132 (1995)

[Publications] Y.Tsutsumi: "Molecular design of hybrid tumor necrosis factor-α with polyethylene glycol increases its anti-tumor potency" Brit.J.Cancer. 71. 963-968 (1995)

[Publications] N.Utoguchi: "Isolation and properties of tumor-derived endothelial cells from rat KMT-17 fibrosarcoma" Jpn.J.Cancer Res.86. 193-201 (1995)

[Publications] N.Utoguchi: "Tumor-conditioned medium increases macromolecular permeability of endothelial cell monolayer" Cancer Lett.89. 7-14 (1995)

[Publications] T.Kimura: "Central nervous system depressant effects of N^3-substituted derivatives of deoxyuridine in mice" Biol. Pharm. Bull.19(1). 142-145 (1996)

[Publications] T.Kimura: "Localization of uridine receptor on synaptic membranes" Sleep Res.24A. 128 (1995)

[Publications] J.Watanabe: "Uptake of fractionated ^3 H-heparin by isolated rat Kupffer cells" Pharm.Res.12. 1092-1095 (1995)

[Publications] J.Watanabe: "Uptake of low molecular weight fractionated 〔^3H〕 heparin by rat hepatocytes in the primary culture" Biol. Pharm. Bull.18. 443-446 (1995)

[Publications] Y.Sai: "Immunolocarization and pharmacological relevance of oligopeptide transporter PepT1 in intestinal absorption of β-lactam antibiotics" FEBS Lett.392(1). 25-29 (1996)

[Publications] J.Komura: "Na^+ and Cl^- dependent transport of β-alanine across the blood-brain barrier" J.Neurochem.67(1). 330-305 (1996)

[Publications] K.Miyamoto: "Sequence,tissue distribution and developmental changes in rat intestinal oligopeptide transporter" Biochim. Biophys. Acta. 1305(1). 34-38 (1996)

[Publications] A.Tsuji: "Carrier-mediated intestinal transport of drugs" Pharm.Res.13(7). 963-977 (1996)

[Publications] I.Tamai: "Carrier-mediated approaches for oral drug delivery" Adv.Drug Delivery Rev.20. 5-32 (1996)

[Publications] I.Tamai: "Drug delivery through the blood-brain barrier" Adv.Drug Delivery Rev.19. 401-424 (1996)

[Publications] T.Ogihara: "Stereoselective and carrier-mediated transport of monocarboxylic acids across Caco-2 cells" Pharm.Res.13(12). 1828-1832 (1996)

[Publications] T.Terao: "Active secretion of drugs from the small intestinal epithelium in rats by P-glycoprotein functioning as as absorption barrier" J.Pharm. Pharmacol.48. 1083-1089 (1996)

[Publications] T.Minagawa: "Blood-brain-barrier transport of lipid microspheres containing clinoprost,a prostaglandin I2 analogue" J.Pharm. Pharmacol.48. 1016-1022 (1996)

[Publications] M.Tomita: "Absorption-enhancing mechanism of EDTA,caprate,and decanyolcarnitine in Caco-2 cells" J.Pharm. Sci.85(6). 608-611 (1996)

[Publications] T.Ohtomo: "Transport of levofloxacin in a kidney epithelial cell line,LLC-PK 1: Interaction with organic cation transporters in apical and basolateral membranes" J.Pharmacol. Exp.Ther.276(3). 1143-1148 (1996)

[Publications] H.Ogihara: "Immuno-localization of N^+/peptide cotransporter in rat digestive tract" Biochem. Biophys. Res.Commun.220(3). 848-852 (1996)

[Publications] H.Saito: "Molecular cloning and tissue distribution of rat peptide transporter PEPT2" Biochim. Biophys. Acta. 1280(2). 173-177 (1996)

[Publications] K.Tanaka: "Effect of cyclosporin analogues and FK506 on transcellular transport of daunorubicin and vinblastine via P-glycoprotein" Pharm.Res.13(7). 1073-1077 (1996)

[Publications] T.Nabekura: "Modulation of organic cation transport and lipid fluidity by benzyl alcohol in rat renal brush-border membranes" Pharm.Res.13(7). 1069-1072 (1996)

[Publications] M.Okuda: "cDNA cloning and functional expression of a novel rat kidney organic cation transporter,OCT2" Biochem. Biophys. Res.Commun.224(2). 500-507 (1996)

[Publications] H.Saito: "Cloning and functional characterization of a novel rat organic anion transporter mediating basolateral uptake of methotrexate in the kidney" J.Biol.Chem.271(34). 20719-20725 (1996)

[Publications] M.Takano: "Regulation of p-aminohippurate transport by protein kinase C in OK kidney epithelial cells" Am.J.Physiol.271(2). F469-F475 (1996)

[Publications] T.Nabekura: "Cholesterol modulates organic cation transport activity and lipid fluidity in rat renal brush-border membranes" Biochim. Biophys. Acta. 1283(2). 232-236 (1996)

[Publications] T.Terada: "Identification of the histidine residues involved in substrate recognition by rat H^+/peptide cotransporter. PEPT1" FEBS Lett.394(2). 196-200 (1996)

[Publications] H.Saito: "Na^+-Dependent uptake of 1,5-anhydro-D-glucitol via the transport systems for D-glucose and D-mannose in kidnev epithelial cell line. LLC-PK1" Jpn.J.Nephrology.38(10). 435-440 (1996)

辻彰金沢大学, 薬学部, 教授 (10019664)

[Publications] 辻彰: "薬物相互作用-P糖蛋白質" ファルマシア. 31. 997-1001 (1995)

[Publications] 乾賢一: "腎臓学-病態生理からのアプローチ" 南江堂, 442 (1995)