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), was studied in Caco-2 cell monolayers and rat intestinal tissue mounted in Ussing chambers. In both experimental methods, PAH exhibited vectorial transport with significantly greater permeability in the secretory direction than the absorptive direction, indicating net secretion. This secretory transport required metabolic energy, but protons or hydroxyl ions were not involved as the driving force. In Caco-2 monolayers, secretory transport of [3H]PAH was decreased, and the intracellular accumulation of PAH was increased with increasing concentration of unlabelled PAH at the basolateral side. Addition of probenecid and genistein at the basolateral side decreased the secretory transport of [3H]PAH; the accumulation was not changed by probenecid, but was increased by genistein. In addition, the initial uptake rate of [3H]PAH from the basolateral side was decreased by both PAH and probenecid, but not by genistein. Therefore, it is suggested that the transport of PAH in Caco-2 cells is regulated by several transporters: a genistein-sensitive transporter on the apical membrane and probenecid-sensitive transporters on both the basolateral and apical membranes. In rat intestinal tissues, the transport rate of PAH showed regional variation (ileum > jejunum > duodenum), suggesting 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 intestinal tissues is regulated by multiple transporters on the apical and basolateral membranes, and these transporters have different characteristics.
Naruhashi
K
K
Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.
Tamai
I
I
Sai
Y
Y
Suzuki
N
N
Tsuji
A
A
D000818:Animals; D001692:Biological Transport; D018938:Caco-2 Cells / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D004064:Digestive System / Q000166:cytology / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D011339:Probenecid / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014528:Uricosuric Agents / Q000494:pharmacology; D010130:p-Aminohippuric Acid / Q000493:pharmacokinetics*
D004791:Enzyme Inhibitors; D014528:Uricosuric Agents; D019833:Genistein; D011339:Probenecid; D010130:p-Aminohippuric Acid