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Abstract

Enhanced transepithelial flux of cimetidine by Madin-Darby canine kidney cells overexpressing human P-glycoprotein.

B F Pan, A Dutt and J A Nelson
Journal of Pharmacology and Experimental Therapeutics July 1994, 270 (1) 1-7;
B F Pan
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A Dutt
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J A Nelson
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Abstract

Cimetidine has been used as a relatively selective inhibitor of renal organic cation secretion, analogous to the use of probenecid to inhibit organic anion secretion. Many of the substrates for the multidrug transporter P-glycoprotein, which is overexpressed in multidrug-resistant tumor cells, are organic cations. Furthermore, the protein is normally expressed on the apical membranes of proximal tubule cells, the postulated site for active organic cation secretion. To test directly whether P-glycoprotein might serve as a carrier for cimetidine, we measured cimetidine transepithelial movement across Madin-Darby canine kidney cells grown as monolayers on membrane filters. A retrovirally transduced Madin-Darby canine kidney cell line (Madin-Darby canine kidney cells transfected with the human multiple drug resistance 1 cDNA for P-glycoprotein), that expresses the human form of P-glycoprotein on its apical membrane, had an increased capacity to transport cimetidine from the basolateral to apical medium (b-->a) but not in the reverse direction (i.e., a-->b). Qualitatively similar results were observed with daunomycin, a well established substrate for P-glycoprotein. Cellular uptake and energy-dependent efflux experiments further established cimetidine to be a substrate for the human P-glycoprotein. Thus, P-glycoprotein may play a role in the renal secretion of cimetidine and perhaps other organic cations.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 270, Issue 1
1 Jul 1994
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Abstract

Enhanced transepithelial flux of cimetidine by Madin-Darby canine kidney cells overexpressing human P-glycoprotein.

B F Pan, A Dutt and J A Nelson
Journal of Pharmacology and Experimental Therapeutics July 1, 1994, 270 (1) 1-7;

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Abstract

Enhanced transepithelial flux of cimetidine by Madin-Darby canine kidney cells overexpressing human P-glycoprotein.

B F Pan, A Dutt and J A Nelson
Journal of Pharmacology and Experimental Therapeutics July 1, 1994, 270 (1) 1-7;
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