pgp - publications

Predict more pgp - ligand interactions now!

1. Biochem Biophys Res Commun. 2012 Feb 7. [Epub ahead of print]

Real-time analysis of P-glycoprotein-mediated drug transport across primary
intestinal 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 and
Dental 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 vitro
experimental 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 the
apical membrane were observed in the small intestinal epithelium grown as cystic
organoids. Rhodamine123 (Rh123), a substrate for P-gp, was actively transported
in the basoapical direction and accumulated in the luminal space, while the
epithelial integrity was kept intact. Furthermore, we were able to monitor the
whole process of Rh123 transport and its inhibition by verapamil in real-time,
from which kinetic parameters for Rh123 transport could be estimated by a
mathematical modeling. The method here described to evaluate the dynamics of
P-gp-mediated transport in primary intestinal epithelial cells would be
instrumental in investigating the physiological function of P-gp and its
inhibitors/inducers in vitro.

Copyright © 2012. Published by Elsevier Inc.

PMID: 22342245 [PubMed - as supplied by publisher]