Factors in Cell Membrane Transport and Tissue Distribution of Drugs

血浆白蛋白介导离体大鼠肝细胞对溴磺酞的摄取。白蛋白与肝细胞的结合行为揭示了它们之间的非特异性相互作用，表明肝细胞上不存在“白蛋白受体”。白蛋白与肝细胞的相互作用引起了白蛋白和细胞膜的结构变化，通过ESR、差异吸收光谱和荧光去极化检测。此外，白蛋白还能增加细胞膜的通透性。脂质体的渗透性证明了这一点。研究了吸收促进剂对肠道细胞旁和跨细胞途径的影响。启动子增强了水和药物的吸收。瓦巴因抑制EDTA、牛磺胆酸（TC）、癸酸（C10）等细胞旁启动子对药物和水分的吸收。吸水率的增加与吸收部位血流量的增加有关。在旁细胞机制中，C10、C12和混合胶束（油酸和TC）扩大了水通道的膜孔，使菊粉通过膜孔渗透。在跨细胞机制上，上述启动子与膜蛋白和膜脂相互作用，引起膜扰动，增加膜通透性。结果表明，许多有效的启动子是细胞旁启动子，也增加了跨细胞通透性。通过Sephadex G-75（超细）凝胶过滤和色谱聚焦，从大鼠骨骼肌细胞质中分离出一种酸性物质结合蛋白fI-protein。该蛋白定位于肌肉间质液，含2.4 mg/g组织，分别通过荧光抗体技术和径向免疫扩散法测定。乌氏双免疫扩散表明，fi -蛋白与各分离白蛋白具有免疫学上的同一性，分离过程与fi -蛋白相同，fi -蛋白在结合亲和力、理化性质和免疫学特性上与白蛋白相似。然而，其分离谱与白蛋白不同，表明fi蛋白起源于肌肉。少

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