Expression and function of p-glycoprotein in a mouse kidney cell
line..
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 2:0088C, 1995.
P-Glycoprotein (PGP)1, a transporter conferring multidrug resistance
to cancer cells, is expressed in the kidney. C219 mAb binding
revealed PGP in proximal tubules and mesangium of mouse kidneys. A
cell line (TKPTS) expressing PGP was developed from proximal tubules
of the 8Tg(SV40E)Bri7 mouse. Northern blot analysis demonstrated a
5.0 Kb message identified as mdr1 by RNase protection assay. 0.15 and
10 [mu]M cyclosporin A (CSA) increased cellular accumulation of
verapamil (VRP) by 32 and 121%, respectively (p<0.001). 5 [mu]M VRP
increased steady-state cellular accumulation of CSA by 46% (P=0.02).
Basal-to-apical transport of the PGP substrate Vinblastine was
inhibited by VRP. R123 influx was rapid and independent of PGP. R123
efflux was inhibited by VRP and CSA. Inhibition of PGP transport by
VRP, CSA and PSC-833 decreased the ED50 of adriamycin. The
concomitant administration of VRP and CSA was not deleterious and
coincided with preferential accumulation of VRP over CSA. Inhibition
of PGP-mediated transport is demonstrated as a mechanism of renal
cell toxicity.
Received 3 November 1994; accepted in final form 31 January 1995.
APS Manuscript Number C657-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 28 February 1995.