Secretory transport of p-aminohippuric acid across intestinal epithelial cells in Caco-2 cells and isolated intestinal tissue

The intestinal transport of an organic anion, p-aminohippuric acid (PAH), w as studied in Caco-2 cell monolayers and rat intestinal tissue mounted in U ssing chambers. In both experimental methods, PAH exhibited vectorial transport with signif icantly greater permeability in the secretory direction than the absorptive direction, indicating net secretion. This secretory transport required met abolic energy, but protons or hydroxyl ions were not involved as the drivin g force. In Caco-2 monolayers, secretory transport of [H-3]PAH was decrease d, and the intracellular accumulation of PAH was increased with increasing concentration of unlabelled PAH at the basolateral side. Addition of proben ecid and genistein at the basolateral side decreased the secretory transpor t of [H-3]PAH; the accumulation was not changed by probenecid, but was incr eased by genistein. In addition, the initial uptake rate of [H-3]PAH from t he basolateral side was decreased by both PAH and probenecid, but not by ge nistein. Therefore, it is suggested that the transport of PAH in Caco-2 cel ls is regulated by several transporters: a genistein-sensitive transporter on the apical membrane and probenecid-sensitive transporters on both the ba solateral and apical membranes. In rat intestinal tissues, the transport ra te of PAH showed regional variation (ileum > jejunum > duodenum), suggestin g that secretory transporters with high activity exist predominantly in the lower region of the small intestine. The results suggest that PAH transport in both Caco-2 cells and rat intesti nal tissues is regulated by multiple transporters on the apical and basolat eral membranes, and these transporters have different characteristics.