APStracts 2:0378C, 1995.

Xenobiotic transport differences in mouse mesangial cell clones expressing mdr1 and mdr3. Ernest, Sylvain, and Elsa Bello-Reuss. Department of Internal Medicine and Department of Physiology and Biophysics, University of Texas Medical Branch, Galveston, Texas 77555

APStracts 2:0378C, 1995.

P-glycoprotein (PGP), which confers multidrug resistance to cancer cells, is expressed in mouse kidney proximal tubule and mesangium. We report now on the expression of PGP and its xenobiotic transport function in mesangial cells. Studies were performed in a mouse mesangial cell line (TKGM) and two cell clones. RNase protection assay and Western blot analysis demonstrated that TKGM cells expressed mdr1 and mdr3, the isoforms responsible for multidrug resistance. TKGM-F12 cells coexpressed mdr1 and mdr3 whereas TKGM-G2 cells only expressed mdr1. The drug transport function, measured by Rhodamine 123 (R123) efflux, was smaller in TKGM-F12 than in TKGM-G2 cells. The PGP substrates adriamycin, cyclosporin A, vinblastine, and verapamil inhibited R123 transport in TKGM and TKGM-G2 cells. In the cells studied PGP conferred some resistance to adriamycin; concomitant exposure to adriamycin with another PGP substrate impaired cell growth. The differential expression of mdr1 and mdr3 in mouse mesangial cell clones, the ability of mdr1 PGP to transport R123, and the impairment of PGP-mediated transport in TKGM-F12 cells, coexpressing mdr1 and mdr3 products, are demonstrated. PGP may play a physiological role in mesangial cells.

Received 24 April 1995; accepted in final form 15 September 1995.
APS Manuscript Number C226-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95