Drug accumulation in the presence of the multidrug resistance pump: dissociation between verapamil accumulation and the action of P-glycoprotein

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Drug accumulation in the presence of the multidrug resistance pump : dissociation between verapamil accumulation and the action of P-glycoprotein. / Ayesh, S; Litman, Thomas; Stein, W D.

In: Receptors and Channels, Vol. 5, No. 3-4, 1997, p. 175-83.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Ayesh, S, Litman, T & Stein, WD 1997, 'Drug accumulation in the presence of the multidrug resistance pump: dissociation between verapamil accumulation and the action of P-glycoprotein', Receptors and Channels, vol. 5, no. 3-4, pp. 175-83.

APA

Ayesh, S., Litman, T., & Stein, W. D. (1997). Drug accumulation in the presence of the multidrug resistance pump: dissociation between verapamil accumulation and the action of P-glycoprotein. Receptors and Channels, 5(3-4), 175-83.

Vancouver

Ayesh S, Litman T, Stein WD. Drug accumulation in the presence of the multidrug resistance pump: dissociation between verapamil accumulation and the action of P-glycoprotein. Receptors and Channels. 1997;5(3-4):175-83.

Author

Ayesh, S ; Litman, Thomas ; Stein, W D. / Drug accumulation in the presence of the multidrug resistance pump : dissociation between verapamil accumulation and the action of P-glycoprotein. In: Receptors and Channels. 1997 ; Vol. 5, No. 3-4. pp. 175-83.

Bibtex

@article{e46f81cf90494057835513976f44d4aa,
title = "Drug accumulation in the presence of the multidrug resistance pump: dissociation between verapamil accumulation and the action of P-glycoprotein",
abstract = "We studied the interaction between the multidrug transporter, P-glycoprotein, and two compounds that interact with it: vinblastine, a classical substrate of the pump, and verapamil, a classical reverser. Steady-state levels of accumulation of these two drugs were determined in a multidrug resistant P388 leukemia cell line, P388/ADR. The time course of accumulation of these drugs, and the effect of energy starvation and the presence of chloroquine on the level of their steady-state accumulation were quite disparate. Vinblastine inhibited the accumulation of verapamil whereas it enhanced the accumulation of daunomycin, another classic substrate of P-glycoprotein. Verapamil did not compete with the intracellular binding sites of vinblastine. In all these aspects, vinblastine behaved as a typical substrate of P-glycoprotein but verapamil did not. Our data suggest that verapamil is a reverser of P-glycoprotein but that its intracellular accumulation is not affected by this membrane-bound transporter.",
keywords = "Animals, Antineoplastic Agents, Phytogenic, Chloroquine, Daunorubicin, Drug Resistance, Multiple, Mice, P-Glycoprotein, Tumor Cells, Cultured, Verapamil, Vinblastine",
author = "S Ayesh and Thomas Litman and Stein, {W D}",
year = "1997",
language = "English",
volume = "5",
pages = "175--83",
journal = "Receptors and Channels",
issn = "1060-6823",
publisher = "Taylor & Francis",
number = "3-4",

}

RIS

TY - JOUR

T1 - Drug accumulation in the presence of the multidrug resistance pump

T2 - dissociation between verapamil accumulation and the action of P-glycoprotein

AU - Ayesh, S

AU - Litman, Thomas

AU - Stein, W D

PY - 1997

Y1 - 1997

N2 - We studied the interaction between the multidrug transporter, P-glycoprotein, and two compounds that interact with it: vinblastine, a classical substrate of the pump, and verapamil, a classical reverser. Steady-state levels of accumulation of these two drugs were determined in a multidrug resistant P388 leukemia cell line, P388/ADR. The time course of accumulation of these drugs, and the effect of energy starvation and the presence of chloroquine on the level of their steady-state accumulation were quite disparate. Vinblastine inhibited the accumulation of verapamil whereas it enhanced the accumulation of daunomycin, another classic substrate of P-glycoprotein. Verapamil did not compete with the intracellular binding sites of vinblastine. In all these aspects, vinblastine behaved as a typical substrate of P-glycoprotein but verapamil did not. Our data suggest that verapamil is a reverser of P-glycoprotein but that its intracellular accumulation is not affected by this membrane-bound transporter.

AB - We studied the interaction between the multidrug transporter, P-glycoprotein, and two compounds that interact with it: vinblastine, a classical substrate of the pump, and verapamil, a classical reverser. Steady-state levels of accumulation of these two drugs were determined in a multidrug resistant P388 leukemia cell line, P388/ADR. The time course of accumulation of these drugs, and the effect of energy starvation and the presence of chloroquine on the level of their steady-state accumulation were quite disparate. Vinblastine inhibited the accumulation of verapamil whereas it enhanced the accumulation of daunomycin, another classic substrate of P-glycoprotein. Verapamil did not compete with the intracellular binding sites of vinblastine. In all these aspects, vinblastine behaved as a typical substrate of P-glycoprotein but verapamil did not. Our data suggest that verapamil is a reverser of P-glycoprotein but that its intracellular accumulation is not affected by this membrane-bound transporter.

KW - Animals

KW - Antineoplastic Agents, Phytogenic

KW - Chloroquine

KW - Daunorubicin

KW - Drug Resistance, Multiple

KW - Mice

KW - P-Glycoprotein

KW - Tumor Cells, Cultured

KW - Verapamil

KW - Vinblastine

M3 - Journal article

C2 - 9606721

VL - 5

SP - 175

EP - 183

JO - Receptors and Channels

JF - Receptors and Channels

SN - 1060-6823

IS - 3-4

ER -

ID: 119647821