Drug accumulation in the presence of the multidrug resistance pump: dissociation between verapamil accumulation and the action of P-glycoprotein
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
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.
I: Receptors and Channels, Bind 5, Nr. 3-4, 1997, s. 175-83.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
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