1993 Fiscal Year Final Research Report Summary
Pharmacokinetic Study on Mucopolysaccharide : Effect of Plasma Protein on the Hepatic Uptake of fractionated Heparin
| Project/Area Number |
04671328
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Physical pharmacy
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| Research Institution | Nagoya City University |
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Principal Investigator |
WATANABE Jun Nagoya City University, Faculty of Pharmaceut. sci. Professor, 薬学部, 教授 (80080175)
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| Co-Investigator(Kenkyū-buntansha) |
HABA Masami Nagoya City University, Faculty of Pharmaceut. sci. Assoc. Professor, 薬学部, 助手 (70254307)
YUASA Hiroaki Nagoya City University, Faculty of Pharmaceut. sci. Assoc. Professor, 薬学部, 助教授 (20191471)
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| Project Period (FY) |
1992 – 1993
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| Keywords | rat parenchymal hepatocyte / fractionated heparin / dose-dependent uptake / transport inhibitor / anion transport system / plasma protein / a-globulin / albumin |
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| Research Abstract |
(1) The uptake rate of fractionated [^3H]heparin by rat parenchymal hepatocytes was concentration-dependent and found to be expressed by a Michaelis-Memten equation.
(2) The uptake was not inhibited by the inhibitor of receptor-mediated endocytosis, pohenylarsine oxide, but it was inhibited hoth by an inhibitor of the anion transprtt system, DIDS and by an anion, rose bengal.
(3) Interelization o ffractionnated heparin was confirmed with FITC-fractionated heparin using confocal imaging wywtem with an inverted flurorescence microscope.
(4) After intravenous administration of fractionated [^3H]heparin the uptake rates of radioactivity by parenchymal non-parenchymal cells were dose-dependent, and the dose-dependency was more remarkable in the uptake by non-parenchymal cells.
(5) The uptake clearances for both parenchymal and non-parenchymal cells were considerablly larger than that for PVP(polyvinylpyrorifon), suggesting that the fractionated peparin was taken up by the other mechaniasm than fluid phase encocytosis.
(6) The interaction of fractionated [^3H]heparin with a-globulin was greater than that with albumin.
(7) a-Globulin showed the decreasing effect on the hepatic uptake clearance of fractionated [^3H]heparin in the perfused rat liver, and "protein-mediated transport" was involved in the uptake. On the other hand albumin did not affect the uptake process.
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