Uptake Mechanism of Fractionated [^3H]Heparin in Rat Parenchymal Hepatocytes in Primary Culture : Effect of Transport Inhibitors on the Uptake
スポンサーリンク
概要
- 論文の詳細を見る
In order to elucidate the uptake mechanism of fractionated [^3]heparin by rat parenchymal hepatocytes, the concentration dependent uptake was kinetically analyzed in primary culture of rat parenchymal hepatocytes, and the effects of established transport inhibitors and heparin analogues on the uptake were also examined. The uptake rate of heparin measured over an extended period of 60 min was saturable, with the maximum uptake velocity (V_<max>) of 0.36±0.05 pmol/min/mg protein and the Michaelis constant (K_m) of 21.2±5.4 nM. The uptake was inhibited by the addition of 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), and inhibitor of the anion transport system, and rose bengal, an organic anion. Heparin analogues (pentosan polysulphate, or heparan sulphate) also inhibited the uptake of fractionated heparin. However, the uptake was not inhibited by the inhibitors of receptor-mediated endocytosis (phenylarsine oxide). These results suggest that fractionated heparin may be taken up by anion transport system, rather than by receptor-mediated endocytosis, though the fractionated [^3H]heparin is a compound with the high molecular weight of about 20000 Da. At least the negative charge or sulphate group in the drug structure is supposed to play an important role in the uptake of fractionated heparin by parenchymal hepatocytes.
- 社団法人日本薬学会の論文
- 1993-05-15
著者
-
渡邊 淳
名古屋市立大学・薬
-
渡邊 淳
Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Nagoya City University
-
村西 廣哉
Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Nagoya City University
-
湯浅 博昭
Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Nagoya City University
-
村西 廣哉
Department Of Biopharmaceutics Faculty Of Pharmaceutical Sciences Nagoya City University
関連論文
- Macromolecule-Macromolecule Interaction in Drug Distribution. III. Kinetic Characterization of the Uptake of Fractionated [^3H]Heparin and the Effect of Plasma Proteins in the Perfused Rat Liver
- ラットにおけるリチウムの腸管膜透過機構
- 大腸における[^3H]Inulinの部位特異的分解を利用した小腸通過時間の評価
- ラットにおける小腸-大腸間の膜透過性の比較
- 分画[^3H]Heparinの体内動態における分子量依存性及び投与量依存性
- Uptake of Low Molecular Weight Fractionated [^3H] Heparin by Rat Hepatocytes in the Primary Culture
- Dose-Dependent Uptake of Radioactivity by Liver Parenchymal and Non-parenchymal Cells after Intravenous Administration of Fractionated ^3H-Heparin to Rats
- Uptake of Fluorescein Isothiocyanate (FITC)-Fractionated Heparin by Rat Parenchymal Hepatocytes in Primary Culture
- Uptake Mechanism of Fractionated [^3H]Heparin in Rat Parenchymal Hepatocytes in Primary Culture : Effect of Transport Inhibitors on the Uptake
- Macromolecule-Macromolecule Interaction in Drug Distribution. II. Effect of α-Glubulin on Saturable Uptake of Fractionated [^3H]Heparin by Rat Parenchymal Hepatocytes in Primary Culture