pgp - publications
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1. Biochem Biophys Res Commun. 2012 Feb 7. [Epub ahead of print]Real-time analysis of P-glycoprotein-mediated drug transport across primaryintestinal epithelium three-dimensionally cultured in vitro.Mizutani T, Nakamura T, Morikawa R, Fukuda M, Mochizuki W, Yamauchi Y, Nozaki K, Yui S, Nemoto Y, Nagaishi T, Okamoto R, Tsuchiya K, Watanabe M.Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical andDental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.P-glycoprotein (P-gp) is an efflux transporter that regulates bioavailability of orally administered drugs at the intestinal epithelium. To develop an in vitroexperimental model that mimics P-gp-mediated intestinal drug transport in vivo,we employed normal intestinal epithelium three-dimensionally cultured.Physiological expression of P-gp mRNA and the expression of its protein at theapical membrane were observed in the small intestinal epithelium grown as cystic organoids. Rhodamine123 (Rh123), a substrate for P-gp, was actively transportedin the basoapical direction and accumulated in the luminal space, while theepithelial integrity was kept intact. Furthermore, we were able to monitor thewhole process of Rh123 transport and its inhibition by verapamil in real-time,from which kinetic parameters for Rh123 transport could be estimated by amathematical modeling. The method here described to evaluate the dynamics ofP-gp-mediated transport in primary intestinal epithelial cells would beinstrumental in investigating the physiological function of P-gp and itsinhibitors/inducers in vitro.Copyright © 2012. Published by Elsevier Inc.PMID: 22342245 [PubMed - as supplied by publisher]