胆管結紮ラットにおけるerythromycinとvinblastineの尿中排泄の検討
閉塞性黄疸時には, 胆汁中排泄物質は肝より血中に逆流し, 尿中排泄が主な排泄経路となる. 今回, 胆汁中排泄型のカチオン系薬物であり, 胆汁中排泄にP糖蛋白が関与しているerythromycin(EM)およびvinblastine(VLB)の尿中排泄能を3日間の胆管結紮ラットで検討した.尿中排泄(4時間の累積)は,EMでは対照の1.9±3.6%に比し胆管結紮ラットでは49±5.2%,VLBは対照7.4±2.2%に比し胆管結紮ラットでは18.2±4.7%と,ともに胆管結紮ラットで有意に増加した.胆管結紮ラットでは,通常では役割の少ない尿中排泄が排泄経路として重要となるが,有機カチオンの尿中排泄は...
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| Published in | 胆道 Vol. 16; no. 5; pp. 387 - 391 |
|---|---|
| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
日本胆道学会
2002
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0914-0077 1883-6879 |
| DOI | 10.11210/tando1987.16.5_387 |
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| Abstract | 閉塞性黄疸時には, 胆汁中排泄物質は肝より血中に逆流し, 尿中排泄が主な排泄経路となる. 今回, 胆汁中排泄型のカチオン系薬物であり, 胆汁中排泄にP糖蛋白が関与しているerythromycin(EM)およびvinblastine(VLB)の尿中排泄能を3日間の胆管結紮ラットで検討した.尿中排泄(4時間の累積)は,EMでは対照の1.9±3.6%に比し胆管結紮ラットでは49±5.2%,VLBは対照7.4±2.2%に比し胆管結紮ラットでは18.2±4.7%と,ともに胆管結紮ラットで有意に増加した.胆管結紮ラットでは,通常では役割の少ない尿中排泄が排泄経路として重要となるが,有機カチオンの尿中排泄は物質により異なり,VLBよりもEMの方がその効率が良好であった. |
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| AbstractList | 「要旨」：閉塞性黄疸時には, 胆汁中排泄物質は肝より血中に逆流し, 尿中排泄が主な排泄経路となる. 今回, 胆汁中排泄型のカチオン系薬物であり, 胆汁中排泄にP糖蛋白が関与しているerythromycin(EM)およびvinblastine(VLB)の尿中排泄能を3日間の胆管結紮ラットで検討した. 尿中排泄(4時間の累積)は, EMでは対照の1.9±3.6%に比し胆管結紮ラットでは49±5.2%, VLBは対照7.4±2.2%に比し胆管結紮ラットでは18.2±4.7%と, ともに胆管結紮ラットで有意に増加した. 胆管結紮ラットでは, 通常では役割の少ない尿中排泄が排泄経路として重要となるが, 有機カチオンの尿中排泄は物質により異なり, VLBよりもEMの方がその効率が良好であった. 閉塞性黄疸時には, 胆汁中排泄物質は肝より血中に逆流し, 尿中排泄が主な排泄経路となる. 今回, 胆汁中排泄型のカチオン系薬物であり, 胆汁中排泄にP糖蛋白が関与しているerythromycin(EM)およびvinblastine(VLB)の尿中排泄能を3日間の胆管結紮ラットで検討した.尿中排泄(4時間の累積)は,EMでは対照の1.9±3.6%に比し胆管結紮ラットでは49±5.2%,VLBは対照7.4±2.2%に比し胆管結紮ラットでは18.2±4.7%と,ともに胆管結紮ラットで有意に増加した.胆管結紮ラットでは,通常では役割の少ない尿中排泄が排泄経路として重要となるが,有機カチオンの尿中排泄は物質により異なり,VLBよりもEMの方がその効率が良好であった. |
| Author | 栗原, 裕子 滝川, 一 北條, 誠 高田, 由紀子 笹本, 貴広 田中, 洋行 丸茂, 達之 高柳, もとえ 高森, 頼雪 相磯, 光彦 |
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| References | 7) Hirohashi T, Suzuki S, Takikawa H, Sugiyama Y. ATP-dependent transport of bile salts by rat mult i drug resistance-associated protein 3 (mrp 3). J Biol Chem 2000; 275: 2905-10 5) Lee JM, Trauner M, Soroka CJ, Stieger B, Meier PJ, Boyer JL. Expression of the bile salt e x port pump is maintained after chronic cholestasis i n the rat. Gastroenterology. 2000; 118: 163-72 6) Paulusma CC, Kothe MJ, Bakker CT, et al. Zonal down-regulation and redistribution of the multidrug resistance protein 2 during bile duct ligati o n in rat liver. Hepatology 2000; 31: 684-93 11) Sato A, Takikawa H, Yamanaka M. Effects of organic anions and vinblastine on biliary excretion of erythromycin in rats. Parmacology 1 9 99; 59: 249-56 18)武田理夫, 遠藤仁. 有機カチオントランスポーター, Annual Review 腎臓199994-7 15) Zollner G, Fickert P, Zenz R, et al. Hepatobiliary transporter expression in percutaneou s liver biopsies of patients with cholestatic liver diseases. Hepatology 2001; 33: 633-46 1) Takada Y, Suzuki C, Onishi T, et al. Urinary excretion of bile acids in bile duct-ligated rats. J Hepatobiliary Pancreat Surg 2002; 9 (Suppl. 1): 268 19) Lee J, Azzaroli F, Wang L, et al. Adaptive regulation of bile salt transporters in kidney and l i v er in obstructive cholestasis in the rat. Gastroenterology 2001 121: 1473-84 17)寺田智祐, 乾賢一, 薬物トランスポーターの関与する薬物分布と排泄. 医学のあゆみ2001; 197: 17-21 8) Soroka CJ, Lee JM, Azzaroli F, Boyer JL. Cellular localization and up-regulation of multidrug resistanceassociated protein 3 in hepatocytes and cholangiocytes during obstructive cholestasis in r at liver. Hepatology 2001; 33: 783-91 9) Hirohashi T, Suzuki H, Ito K, et al. Hepatic expression of multidrug resistance-associated p r o teinlike proteins maintained in Eisai hy p erbilirubinemic rats. Mol Pharmacol 1998; 53: 1068-75 20)田中裕滋小林由直, 樋口国博, ほか. ヒト肝および腎近位尿細管培養細胞におけるビリルビンおよび胆汁酸のMultidrug Resistance-associated Proten 2(MRP2)発現に及ぼす影響肝臓2002; 43(SuppI D: A196 21)黒田誠, 小林由直, 田中裕滋, ほか. Eisaihyperbilirubinuriarat(EHBR)の肝及び腎におけるrnultidrug resistance-associatedprotein3(rnrp3)の発現の増強肝臓2002; 43(Suppll): A197 3) Gartung C, Ananthanarayanan M, Rahman MA, et al. Down-regulation of expression and function of the rat liver Nat/bile acid cotransporter in extrahe patic cholestasis. Gastroenterology 1996; 110: 199-209 4) Dumont M, Jacquernin E, D'hont C, et al. Expression of the liver Nat-independent organic anion transporting polypeptide (oatp-1) in rats with bile 46: 390胆道16巻5号(2002)duct ligation. J Hepatol 1997; 27: 1051-6 12) Schrenk D, Gant TW, Presiegger K-H, Silverman JA, Marino PA, Thorgeirson SS. Indu c tion of multidrug resistance gene expression during chole stasis in rats and non-human primates. Hepat o logy 1003; 17: 854-60 22) Little JM, Zimniak P, Radominska A, Lehman P, Lester R. Urinary excretion of lithocholic acid an d its conjugates by the bile duct-ligated rat. H epatology 1991; 14: 690-5 2)高田由紀子, 田中洋行, 北條誠, ほか, 胆管結紮ラットおよびEHBRにおけるpravastatinとtemocapri1の尿中排泄の検討(抄録). 題道2002; 16: 237 14) Donner MG, Keppler D. Up-regulation of basolateral multidrug resistance protein 3 (Mrp 3) i n cholestatic rat liver. Hepatology 2001; 34: 351-9 13) Akita H, Suzuki H, Sugiyama Y. Sinusoidal efflux of taurocholate is enhanced in Mrp 2-deficient rat liver. Pharm Res 2001; 18: 1119-25 10) Takikawa H, Sano N, Fukumura S, Uegaki S, Yamanaka M. Impaired biliary excretion o f organic anions and cations in bile duct-ligated ra t. Int Hepatol Commun 1996; 5: 201-6 16) Shoda J, Kano M, Oda K, et al. The expression levels of plasma membrane transporters in the cholestatic liver of patients undergoing bilia r y drainage and their association with the impai r m ent of biliary secretory function. Am J Ga s troenterol 2002; 96: 3368-78 |
| References_xml | – reference: 8) Soroka CJ, Lee JM, Azzaroli F, Boyer JL. Cellular localization and up-regulation of multidrug resistanceassociated protein 3 in hepatocytes and cholangiocytes during obstructive cholestasis in r at liver. Hepatology 2001; 33: 783-91 – reference: 11) Sato A, Takikawa H, Yamanaka M. Effects of organic anions and vinblastine on biliary excretion of erythromycin in rats. Parmacology 1 9 99; 59: 249-56 – reference: 6) Paulusma CC, Kothe MJ, Bakker CT, et al. Zonal down-regulation and redistribution of the multidrug resistance protein 2 during bile duct ligati o n in rat liver. Hepatology 2000; 31: 684-93 – reference: 22) Little JM, Zimniak P, Radominska A, Lehman P, Lester R. Urinary excretion of lithocholic acid an d its conjugates by the bile duct-ligated rat. H epatology 1991; 14: 690-5 – reference: 2)高田由紀子, 田中洋行, 北條誠, ほか, 胆管結紮ラットおよびEHBRにおけるpravastatinとtemocapri1の尿中排泄の検討(抄録). 題道2002; 16: 237 – reference: 3) Gartung C, Ananthanarayanan M, Rahman MA, et al. Down-regulation of expression and function of the rat liver Nat/bile acid cotransporter in extrahe patic cholestasis. Gastroenterology 1996; 110: 199-209 – reference: 10) Takikawa H, Sano N, Fukumura S, Uegaki S, Yamanaka M. Impaired biliary excretion o f organic anions and cations in bile duct-ligated ra t. Int Hepatol Commun 1996; 5: 201-6 – reference: 17)寺田智祐, 乾賢一, 薬物トランスポーターの関与する薬物分布と排泄. 医学のあゆみ2001; 197: 17-21 – reference: 5) Lee JM, Trauner M, Soroka CJ, Stieger B, Meier PJ, Boyer JL. Expression of the bile salt e x port pump is maintained after chronic cholestasis i n the rat. Gastroenterology. 2000; 118: 163-72 – reference: 15) Zollner G, Fickert P, Zenz R, et al. Hepatobiliary transporter expression in percutaneou s liver biopsies of patients with cholestatic liver diseases. Hepatology 2001; 33: 633-46 – reference: 20)田中裕滋小林由直, 樋口国博, ほか. ヒト肝および腎近位尿細管培養細胞におけるビリルビンおよび胆汁酸のMultidrug Resistance-associated Proten 2(MRP2)発現に及ぼす影響肝臓2002; 43(SuppI D: A196 – reference: 21)黒田誠, 小林由直, 田中裕滋, ほか. Eisaihyperbilirubinuriarat(EHBR)の肝及び腎におけるrnultidrug resistance-associatedprotein3(rnrp3)の発現の増強肝臓2002; 43(Suppll): A197 – reference: 14) Donner MG, Keppler D. Up-regulation of basolateral multidrug resistance protein 3 (Mrp 3) i n cholestatic rat liver. Hepatology 2001; 34: 351-9 – reference: 16) Shoda J, Kano M, Oda K, et al. The expression levels of plasma membrane transporters in the cholestatic liver of patients undergoing bilia r y drainage and their association with the impai r m ent of biliary secretory function. Am J Ga s troenterol 2002; 96: 3368-78 – reference: 13) Akita H, Suzuki H, Sugiyama Y. Sinusoidal efflux of taurocholate is enhanced in Mrp 2-deficient rat liver. Pharm Res 2001; 18: 1119-25 – reference: 1) Takada Y, Suzuki C, Onishi T, et al. Urinary excretion of bile acids in bile duct-ligated rats. J Hepatobiliary Pancreat Surg 2002; 9 (Suppl. 1): 268 – reference: 4) Dumont M, Jacquernin E, D'hont C, et al. Expression of the liver Nat-independent organic anion transporting polypeptide (oatp-1) in rats with bile 46: 390胆道16巻5号(2002)duct ligation. J Hepatol 1997; 27: 1051-6 – reference: 19) Lee J, Azzaroli F, Wang L, et al. Adaptive regulation of bile salt transporters in kidney and l i v er in obstructive cholestasis in the rat. Gastroenterology 2001 121: 1473-84 – reference: 7) Hirohashi T, Suzuki S, Takikawa H, Sugiyama Y. ATP-dependent transport of bile salts by rat mult i drug resistance-associated protein 3 (mrp 3). J Biol Chem 2000; 275: 2905-10 – reference: 12) Schrenk D, Gant TW, Presiegger K-H, Silverman JA, Marino PA, Thorgeirson SS. Indu c tion of multidrug resistance gene expression during chole stasis in rats and non-human primates. Hepat o logy 1003; 17: 854-60 – reference: 18)武田理夫, 遠藤仁. 有機カチオントランスポーター, Annual Review 腎臓199994-7 – reference: 9) Hirohashi T, Suzuki H, Ito K, et al. Hepatic expression of multidrug resistance-associated p r o teinlike proteins maintained in Eisai hy p erbilirubinemic rats. Mol Pharmacol 1998; 53: 1068-75 |
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| Snippet | 閉塞性黄疸時には, 胆汁中排泄物質は肝より血中に逆流し, 尿中排泄が主な排泄経路となる. 今回, 胆汁中排泄型のカチオン系薬物であり, 胆汁中排泄にP糖蛋白が関... 「要旨」：閉塞性黄疸時には, 胆汁中排泄物質は肝より血中に逆流し, 尿中排泄が主な排泄経路となる. 今回, 胆汁中排泄型のカチオン系薬物であり, 胆汁中排泄にP糖蛋白が関... |
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| SubjectTerms | 尿中排泄 胆管結紮ラット 閉塞性黄疸 |
| Title | 胆管結紮ラットにおけるerythromycinとvinblastineの尿中排泄の検討 |
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