Intracellular compartmentation of organic anions and cations during renal secretion

Although plasma membrane events mediating organic anion and cation secretion have been intensively investigated, intracellular events associated with transcellular fluxes of secreted solutes have received much less attention. Recent data obtained through epifluorescence and confocal microscopy in renal tissue of mammals, teleosts, and crustaceans indicates that sequestration within intracellular organelles is intimately Quinacrine involved in secretion of both organic anions (OA) and cations Nocodazole (OC). For OA, one compartment is mitochondrial and a second is smaller and more mobile. OA-loaded vesicles were shown to move in a basolateral-to-apical direction in crustacean urinary bladder. This movement was reversibly blocked by nocodazole, a microtubule-disrupting agent. Furthermore, secretion into the lumen of teleost proximal tubule was also reversibly inhibited by nocodazole. For OA, the small mobile vesicles have yet to be identified or isolated. For OC, a population of acidifying endosomes was identified which accumulated tetraethylammonium (TEA) by TEA/proton exchange. Finally, in cultured monolayers of choroid plexus, an epithelium which transports both OA and OC from cerebrospinal fluid to blood, fusion of vesicles with the basolateral membrane and concomitant release of OC was seen during transepithelial transport. This process was also blocked by nocodazole. The roles of sequestration in transepithelial transport are as yet uncertain, but these data argue that such roles are likely.