Pharmacokinetic Study on Mucopolysaccharide : Effect of Plasma Protein on the Hepatic Uptake of fractionated Heparin

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(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.