Transport mechanisms of drugs in intestinal and renal epithelial cell membranes

Abstract

The isolated plasma membrane vesicles have been widely used as an in vitro model system for studying the transcellular transport of nutrients and electrolytes in the renal tubule and intestine, and the findings have generated a great deal of information about the mechanisms of the absorptive and the secretory processes. Active secretion of organic anions and cations in the proximal tubule is viewed as a means of eliminating many exogeneous drugs and their metabolites from the body. The tubular secretion involves transport across contraluminal basolateral membranes, and accumulation in the epithelial cells, followed by efflux from the cells across luminal brush border membranes into the tubular fluid.The transport of p-aminohippurate(PAH), a prototype anion, and tetraethylammonium(TEA), a prototype cation, has been characterized using brush border and basolateral membrane vesicles. Data suggest that PAH is transported by a carriermediated system(anion exchange mechanism)in basolateral membranes and by a channellike system in brush border membranes. In contrast, TEA is transported across basolateral membranes via carrier-mediated system, and this process is stimulated by an insidenegative membrane potential. TEA transport across brush border membranes is driven by an H+ gradient via electroneutral H+/TEA antiport system. Furthermore, it has been demonstrated that aminocephalosporins such as cephradine and cephalexin, possessing an α-amino group and a carboxyl group, can be transported via a common carrier system with dipeptides in the intestinal and renal brush border membranes and that their transport is driven by an inward H+ gradient. Thus, the vesicle studies provide new insights into our understanding of intestinal and renal tubular transport mechanisms of drugs.