Cellular and molecular mechanisms of renal tubular secretion of organic anions and cations

A wide variety of endogenous organic ions and xenobiotics are secreted into the urine via organic anion and cation transport systems, expressed in brush-border and basolateral membranes of renal tubular cells. Using membrane vesicles isolated from the kidney, cultured renal epithelial cells, isolated renal tubules, and slices of renal cortex, extensive studies have been done regarding the mechanisms of renal tubular secretion of organic ions. Basolateral entry of organic anions is mediated by the organic anion/dicarboxylate exchange system, whereas apical extrusion of organic anions from epithelial cells is mediated by an anion exchanger and/or by membrane potential-sensitive transport systems. Studies using membrane vesicles have made clear the fact that the basolateral transport of organic cations is stimulated by inside-negative membrane potential, whereas the transport of organic cations in brush-border membranes is achieved by a proton gradient. Trasport studies using cultured renal epithelial cells have shown other aspects of organic ion transport, such as regulatory mechanisms for transcellular transport of orgnaic anions and cations. The recent development of molecular techniques has greatly advanced our understanding of the molecular aspects of various transport processes. In 1994, a cDNA clone encoding the prototype organic cation transporter was isolated from rat kidney. Within the last 3 years, several organic anion and cation transporters in the kidney have been identified by different cloning techniques. In this review, we describe the mechanisms mediating renal tubular secretion of organic anions and cations, including recent topics in this area.