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
スポンサーリンク
概要
- 論文の詳細を見る
The uptake of fractionated [^3H]heparin was investigated in rat parenchymal hepatocytes in primary culture. The initial uptake of fractionated [^3H]heparin was found to be saturable with the maximum uptake velocity (V_<max>) of 10.1±1.46 pmol/min/mg protein and the Michaelis constant (K_m) of 284±47.9 nM. The effect of α-globulin, the major protein binding to fractionated [^3H]heparin, on the saturable uptake profile of fractionated [^3H]heparin was also investigated. The uptake clearance was reduced, depending on the concentration of fractionated [^3H]heparin, by the addition of 1 mg/ml α-globulin. We assumed that fractionated ^3H-heparin bound to α-globulin was not available for uptake and that the reduction in the uptake clearance was solely attributable to the saturable binding of fractionated [^3H]heparin to α-globulin. The uptake clearance versus concentration profile was analyzed to obtain the dissociation constant (K_d) of 31.8nM and the capacity (n) of 0.047 for the binding of fractionated [^3H]heparin to α-globulin. The saturable binding of fractionated [^3H]heparin to α-globulin was supported by in vitro binding experiments using gel chromatography, in which bound fractionated [^3H]heparin decreased with the concentration of fractionated [^3H]heparin in the presence of α-globulin. In conclusion, the present study demonstrated the saturable uptake of fractionated [^3H]heparin by rat parenchymal hepatocytes and the saturable binding of fractionated [^3H]heparin to α-globulin. The saturable uptake may suggest the involvement of a specific transport system such as receptor-mediated endocytosis.
- 社団法人日本薬学会の論文
- 1992-11-25
著者
-
渡辺 淳
日本大・薬
-
尾関 昭二
Department of Biopharmaceutics, Faculty of Pharmaceutical Science, Nagoya City University
-
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
-
尾関 昭二
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
- Factors Affecting the in Vitro Stability of ^C-Urea in the Urine of Rats
- Disposition of Urea following Intravenous Administration to Rats
- ソフトカプセル用o/w乳剤タイプ新規基剤の開発 I ビタミンK2含有新規基剤の製剤学的評価
- 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
- Ca 拮抗剤アムロジピンの患者における Population Pharmacokinetics
- ラット小腸におけるニフェジピンの初回通過代謝
- ラット小腸におけるグリセロールの担体輸送機構の解析
- ムコ多糖類のスカベンジャー受容体介在性細胞取り込みの薬物動態学的解析
- ソフトカプセル用o/w乳剤タイプ新規基剤の開発 II 犬におけるビタミンK_2含有新規ソフトカプセル製剤の経口投与後の吸収特性
- 血漿タンパク存在下でのラット培養肝実質細胞における分画 heparin の表面結合と内在化の分子量依存性
- ラット培養肝実質細胞による分画[^3H]Heparin の代謝及び放出の検討
- ラットにおける5-フルオロウラシルの初回通過代謝 : 小腸と肝との相対的寄与
- ラットにおける水溶性低分子薬物の腸管膜透過 : 小腸と大腸との比較および解剖学的要因との関係
- ラット in vivo におけるリボフラビンの非線形消化管吸収の解析
- ラットにおける非線形消化管吸収の生理機構論的解析 : in vitro-in vivo 相関の検討および吸収予測への応用
- 13-6-33 ソフトカプセル用新規基剤の開発
- ラット肝実質細胞における分画heparinの輸送機構:スカベンジャー様レセプターの関与
- 薬物の唾液中排泄(第48報)イヌにおけるトリメタジオンの唾液中排泄 - 最適唾液採取時間の検討 -
- 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
- ラット遊離クッパー細胞による分画ヘパリン輸送機構:スカベンジャー受容体の関与
- 唾液中排泄における変動要因の研究 : TDMと医薬品開発のために
- Difference in Saliva : Plasma Concentration Ratio of Endogenous Urea between Mandibular and Parotid Glands in Dogs
- Role of the Main Mandibular Excretory Duct in Salivary Excretion of Urea in Dogs
- 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
- Macromolecule-Macromolecule Interaction in Drug Distribution : Effect of α-Globulin Concentration on the Hepatic Uptake of Fractionated ^3H-heparin by Perfused Rat Liver
- ラットにおけるリチウムの消化管吸収の制御
- Salivary Excretion of 5-Fluorouracil (5-FU). III. : Non-linear Kinetics of Salivary Excretion of 5-FU Following Bolus Intravenous Administration in Rats
- Dose-Dependent Salivary Excretion Following Bolus Intravenous Administration of Lithium in Dog
- Salivary Excretion of 5-Fluorouracil. I. Fluctuation of the Saliva/Plasma Concentration Ratio and Salivary Clearance in Beagle Dogs Following Bolus Intravenous Administration
- Distribution of Thiourea following Intravenous and Oral Administration to Rats
- Absorption and Distribution of Creatinine and Urea in Hereditary Muscular Dystrophic Mice
- The Effect of Sacrificing Method on the Tissue Concentration of Exogeneous Creatinine in Rats
- 薬物の体内分布決定要因の定量的評価
- Influence of Anesthetic Regimens on the Intestinal Absorption of 5-Fluorouracil in Rats
- Gastric Emptying-Limited Oral Absorption of α-Linolenic Acid Administered as a Milk Fat-Globule Membrane (MFGM) Emulsion in Rats
- Evaluation of Milk Fat-Globule Membrane (MFGM) Emulsion for Oral Administration : Absorption of α-Linolenic Acid in Rats and the Effect of Emulsion Droplet Size
- Inter-organ Relation between Salivary Gland and Kidney in Lithium Excretion. IV. Saturation of Inhibitory Effect of NaCl on Ductal Reabsorption of Li^+ in Beagle Dogs
- Inter-organ Relation between Salivary Gland and Kidney in Lithium Excretion. III. Enhanced Salivary and Systemic Clearance of Li^+ by Oral Administration of NaCl in Dogs
- Salivary Excretion of 5-Fluorouracil (5-FU). V. Effect of 5-FU Concentration in Perfusate on the Salivary Excretion of 5-FU in Perfused Rat Mandibular Gland
- Inter-Strain Differences of Exogeneous Creatinine Disposition in Rats and Mice
- Effect of Hypothermia on the Disposition of Thiourea in Mice
- Elimination of Creatinine Following Intravenous Administration
- Effect of Convulsions Induced by Pentylenetetrazole or Electricity on the Dispositions of Creatinine and Urea in Rats
- Effects of pH, Albumin and Urate on the Inactivation Profile of Rabbit Muscle Creatine Phosphokinase
- Drug Interactions. VII. The Fatty Acid Binding Properties of Bovine Serum Albumin
- Drug Interactions. VI. Binding of 1-Anilinonaphthalene-8-sulfonate with Chlorpromazine
- Drug Interactions. V. Binding of Basic Compounds to Bovine Serum Albumin by Fluorescent Probe Technique
- Drug Interactions. III. Binding to and Displacement from Bovine Serum Albumin of Barbiturates
- Drug Interactions. II. Binding of Some Pyrazolone and Pyrazolidine Derivatives to Bovine Serum Albumin
- Drug Interactions. I. Binding of Ascorbic Acid and Fatty Acid Ascorbyl Esters to Bovine Serum Albumin
- Studies on the Stability of Ascorbic Acid. V. Critical Micelle Concentration of Ascorbyl Monofatty Acid Esters
- Influence of Urethane Anesthesia and Abdominal Surgery on Gastrointestinal Motility in Rats