Dose-dependent uptake of radioactivity by liver parenchymal and non-parenchymal cells after intravenous administration of fractionated 3H-heparin to rats.
The dose-dependent uptake of fractionated 3H-heparin in the subpopulations of liver cells, parenchymal and non-parenchymal cells, was characterized in rats in vivo. Following the intravenous administration of fractionated 3H-heparin, the radioactivity in plasma was eliminated according to the first order kinetics at each dose. However, the elimination rate constant decreased with dose over the dose range of 0.3 to 100 U/kg, suggesting nonlinear elimination. In accordance with the delay in the plasma elimination, the uptake rate constant of radioactivity by parenchymal as well as non-parenchymal cells of liver, the major distribution organ, also decreased. Although heparin has long been considered to be taken up by a reticuloendothelial system (RES) such as non-parenchymal cells in the liver, the uptake of fractionated 3H-heparin by parenchymal cells was found to be comparable with that by non-parenchymal cells at the lowest dose of 0.3 U/kg, and even larger than that by non-parenchymal cells at the highest dose of 100 U/kg. The uptake clearances of fractionated 3H-heparin at the dose of 0.3 U/kg were 86.4 and 504 ml/10(8) cells/d, respectively, for parenchymal and non-parenchymal cells. These values were much larger than those reported for polyvinylpyrrolidone, which has been suggested to be taken up by fluid phase endocytosis. Thus, the present study revealed the significant contribution of parenchymal cells in the hepatic uptake of fractionated 3H-heparin. The dose-dependent uptake with high clearance values in both parenchymal and non-parenchymal cells provides an in vivo suggestion of the specialized transport of fractionated heparin in these two subpopulations of liver cells.
Watanabe
J
J
Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Nagoya City University, Japan.
Haba
M
M
Muranishi
H
H
Yuasa
H
H
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006493:Heparin / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014316:Tritium
D014316:Tritium; D006493:Heparin