Factors in Cell Membrane Transport and Tissue Distribution of Drugs

药物细胞膜转运和组织分布的因素

• 批准号: 59460197
• 负责人: AWAZU Shoji
• 金额: $ 4.99万
• 依托单位: Tokyo College of Pharmacy
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1984
• 资助国家: 日本
• 起止时间: 1984 至 1986
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-59460197/
• 关键词: hepatocyte; Albumin; membrane permeability; absorption promoter; paracellular route; transcellular route; binding protein; 骨格筋

Plasma albumin mediated the uptake of bromosulfophthalein into the isolated rat hepatocytes. The binding behabiour of albumin to hepatocytes revealed non-specific interaction between them, suggesting that there is not an "albumin-receptor" on the hepatocytes. The interaction of albumin with the hepatocyte induced structural changes in both albumin and the cell membrane, which were detected by ESR, difference absorption spectra and fluorescence depolarization. Furthermore, albumin is capable of inceeasing the membeane permeability. This was demonstrated in the permeability of liposomes.The effects of absorption promoters on paracellular and transcellular routes in intestinal membrane were investigated. Promoters enhanced the absorption of water as well as drugs. Ouabain suppressed the drug and water absorption by paracellular promoters such as EDTA, taurocholic acid(TC) and capric acid(C10). The increase in water absorption related to that in absorption site blood flow. For paracellular … More mechanism, C10, C12 and mixed micelles (oleic acid and TC) enlarged the membrane pores in water channel and enavled inulin to permeate through them. For transcellular mechanism, the above promoters interacted with membrane protein and lipid, and caused the membrane perturbation to increase the membrane permeability. Consequently, it was shown that many effective promoters are paracellular ones and also increase the transcellular permeability.fI-protein, a binding protein for acidic substances, was isolated from the cytosol of rat skeletal muscles by Sephadex G-75 (superfine) gel filtration and chromatofocusing. This protein localizes in the interstitial fluid of the muscle and is contained 2.4 mg/g-tissue, determined by fluorescent antibody technique and radial immunodiffussion method, respectively. Ouchterlony double-immunodiffusion indicated that fI-protein was an immunological identity with each fractionated albumin, which was separated by the same procedure as that of fI-protein, fI-protein is like albumin in binding affinity, physicochemical and immunological characteristics. However, the separation profile differs from that of albumin, suggesting that fI-protein originates in the muscle. Less

血浆白蛋白介导溴磺酞进入离体大鼠肝细胞的摄取。白蛋白与肝细胞的结合行为表明它们之间存在非特异性相互作用，提示肝细胞上不存在“白蛋白受体”。白蛋白与肝细胞的相互作用引起白蛋白和细胞膜结构的变化，这是检测ESR，差吸收光谱和荧光去极化。此外，白蛋白还能增加膜的通透性。考察了不同吸收促进剂对脂质体在肠膜中的细胞旁和跨细胞途径的影响。促进剂增强了水和药物的吸收。哇巴因通过细胞旁促进剂如EDTA、牛磺胆酸（TC）和癸酸（C10）抑制药物和水的吸收。水吸收的增加与吸收部位血流量的增加有关。对于细胞旁 ...更多信息 C10、C12及油酸和TC混合胶束扩大了水通道中的膜孔，并促使菊粉通过膜孔。在跨细胞机制中，上述启动子与膜蛋白和脂质相互作用，引起膜扰动，增加膜通透性。因此，许多有效的启动子是旁细胞启动子，也能增加跨细胞渗透性。fI蛋白是一种酸性物质的结合蛋白，通过SephadexG-75（超细）凝胶过滤和层析聚焦从大鼠骨骼肌细胞质中分离得到。该蛋白定位于肌肉的间质液中，用荧光抗体技术和放射免疫扩散法分别测定其含量为2.4mg/g组织。Ouchterlony免疫双扩散试验表明，fI蛋白与各分级分离的白蛋白具有免疫学上的同一性，其结合亲和力、理化性质和免疫学特性与白蛋白相似。然而，分离特征与白蛋白不同，表明fI蛋白起源于肌肉。少

项目成果

水間俊: J.Pharmacobio-Dyn.8. 90-94 (1985)

Shun Mizuma：J.Pharmacobio-Dyn.8。90-94 (1985)

梶井寛: J.Pharm.Sci.75. 475-478 (1986)

梶井宏：J.Pharm.Sci.75（1986）。

Masaharu Shiga: "Promotion of Drug Rectal Absorption Related to Water Absorption" Chem. Pharm. Bull.34. 2254-2256 (1986)

Masaharu Shiga：“促进与吸水相关的药物直肠吸收” Chem。

Masaharu Shiga: "Differences in the Promotion Mechanism of the Colonic Absorption of Antipyrine, Phenol Red and Cefmetazole" J. Pharm Pharmacol.39. 118-123 (1987)

Masaharu Shiga：“安替比林、酚红和头孢美唑结肠吸收促进机制的差异”J. Pharm Pharmacol.39。

Hiroshi Kajii: "Fluorescence Study on the Interaction of Salicylate with Rat Small Intestinal Epithelial Cells: Possible Mechanism for the Promoting Effects of Salicylate on Drug Absorption In Vivo" Life Sci.37. 523-530 (1985)

Hiroshi Kajii：“水杨酸盐与大鼠小肠上皮细胞相互作用的荧光研究：水杨酸盐促进体内药物吸收作用的可能机制”Life Sci.37。