Structure and Function of Drug Transporters in the Intestinal and Renal Epithelial Cells

我们对H^+/有机阳离子逆向转运蛋白等药物转运蛋白的细胞和分子机制进行了研究肾刷状缘膜和H^+/二肽协同转运蛋白中的（分泌）1）H^+/有机阳离子反向转运蛋白和H^+/二肽协同转运蛋白的底物特异性：抗癌药物bestatin是一种含有不常见氨基酸的二肽，通过H^+/二肽共转运蛋白在肠道刷状缘膜中转运，以及通过肾刷状缘膜中的H^+/有机阳离子逆向转运体和H^+/二肽共转运体。2）肾上皮细胞系LLC-PK_1的有机阳离子跨单层转运：四乙基铵（TEA）从基底外侧逐渐被细胞单层摄取，并单向转运到顶侧。通过降低顶端侧的pH刺激TEA的基底侧向顶端运输。TEA从细胞单层流出到顶侧导致细胞内pH降低。3）口服头孢菌素和Bestatin通过人肠上皮细胞系Caco-2的单层的跨细胞转运：口服头孢菌素通过H^+/二肽协同转运蛋白定位于顶膜，并且特定的转运系统参与了这些抗生素穿过基底外侧膜的外排4）二肽转运蛋白在非洲爪蟾卵母细胞中的表达：在注射来自Caco-2细胞的poly（A）^+mRNA的非洲爪蟾卵母细胞中观察到H^+依赖性二肽转运蛋白的表达。

We have studied the cellular and molecular mechanisms of the drug transporters such as H^+/organic cation antiporter (secretion) in the renal brush-border membranes and H^+/dipeptide cotransporter (absorption) in the intestinal brush-border membranes.1) Substrate Specificity of the H^+/Organic Cation Antiporter and H^+/Dipeptide Cotransporter : Anticancer agent bestatin, a dipeptide containing an unusual amino acid, was transported via the H^+/dipeptide cotransporter in the intestinal brushborder membranes, and via the H^+/organic cation antiporter and the H^+/dipeptide cotransporter in the renal brush-border membranes.2) Transcellular Transport of Organic Cation across Monolayers of Kidney Epithelial Cell Line LLC-PK_1 : Tetraethylammonium (TEA) was taken up progressively by the cell monolayers from the basolateral side, and was transported unidirectionally to the apical side. The basolateral-to-apical transport of TEA was stimulated by lowering pH of the apical side. The TEA efflux from the cell monolayers to the apical side caused a decrease in the intracellular pH.3)Transcellular Transport -of Oral Cephalosporins and Bestatin by Monolayers of Human Intestinal Epithelial Cell Line Caco-2 : Oral cephalosporins accumulated in the Caco-2 cell monolayers via the H^+/dipeptide cotransporter localized in the apical membranes and that a specific transport system was involved in the efflux of these antibiotics across the basolateral membranes.4)Expression of Dipeptide Transporters in Xenopus Oocytes : The expression of H^+-dependent dipeptide transporters was observed in Xenopus laevis oocytes injected with poly (A)^+mRNA from Caco-2 cells.