| Project/Area Number |
15590473
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied pharmacology
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| Research Institution | KINKI UNIVERSITY |
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Principal Investigator |
KAMISAKO Toshinori KINKI UNIVERSITY, School of Medicine, Associate Professor, 医学部, 助教授 (20233934)
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| Co-Investigator(Kenkyū-buntansha) |
OGAWA Hiroshi KINKI UNIVERSITY, School of Medicine, Assistant Professor, 医学部, 講師 (00133546)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2004: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | ABC transporter / MRP2 / MRP3 / cholestasis / bilirubin / bile acid / ethinylestradiol / diosgenin / 薬物輸送蛋白質 / ABCトランスポーター / 臓器相関 |
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| Research Abstract |
Background and Aim : Multidrug resistance protein 2 (Mrp2), Mrp3, bile salt export pump (Bsep) and Mdrlb have been identified as bile acid or drug transporter The purpose of this study is to evaluate hepatic, renal and intestinal ABC transporter expressions during cholestasis. Methods : Experiment 1 : Rats were subjected to bile duct ligation or sham operation. Blood, liver and small intestine were obtained 24 and 72 hours after operation. Experiment 2 : Rats were subjected to four groups as follows : 1)Control group. 2)Diosgenin group (fed with diosgenin in diet [1%(wt/wt)] for seven days). 3)Ethinyl estradiol group (recieved ethinyl estradiol (5mg/kg daily) for five days). 4)Diosgenin-ethinyl estradiol group (received ethinyl estradiol and diosgenin). After treatment, blood, bile, liver and intestine were obtained. The mRNA related to lipid and bile acid metabolism was analyzed by RT-PCR. Results : Intestinal Mrp2 mRNA expression remarkably decreased 24 hours after bile duct and recovered 72 hours after bile duct ligation. Intestinal Mrp3 mRNA expression did not change after BDL. Intestinal Mrp2 mRNA expression was remarkably increased in Diosgenin and Diosgenin-ethinyl estradiol groups in comparison with the control group. There were no significant differences in intestinal Mrp3 mRNA expression among the four groups. Hepatic Mrp3 mRNA expression was remarkably increased in the D, EE and DE groups in comparison with the control group (531 %, 321% and 1160 % of control, respectively, p<0.01). Conclusion : 1)Bile duct ligation affects not only hepatic but also the intestinal Mrp2 expressions. 2)Intestinal Mrp2 mRNA level is regulated by factor in the lumen (e.g. diosgenin feeding). 3)Cholestasis by ethinyl estradiol treatment was enhanced by diosgenin and the increase in hepatic Mrp3 mRNA level may affect the enhancement.
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