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Abstract:
The transport of organic anions in the proximal tubule occurs primarily through the epithelial cells. This process involves movement across both the luminal and contraluminal membranes via specialized transport systems. Although some of the organic anions are taken up into the cell from the lumen, they can also be accumulated in tubule cells from the interstitial compartment by a variety of transporters. The relative affinities of anions for the different luminal and contraluminal transporters in concert with their conjugate driving forces determine the net directional movement, i.e., organic anion absorption or secretion. By use of the approach of stopped-flow microperfusion, it has been possible to characterize the contraluminal anion transporters in the rat. The following three different systems have been identified: 1) an exchange system for sulfate and oxalate; 2) a cotransport system for Na+ and dicarboxylates; and 3) an exchange system (the so-called p-aminohippuric acid transport system) for hydrophobic anions and long-chain fatty acids. By use of a wide variety of different analogues, the substrate specificities for these different systems were determined. Substrates with two negative ionic charges or with one negative ionic charge and one or more negative partial charges interact with all three systems, depending on the distance between the two charged groups. Polyhalogenated substrates are preferred by the dicarboxylate system. Those substrates which interact only with the p-aminohippurate transport system possess a hydrophobic area and one negative ionic charge or two negative partial charges.
