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.
| Original language | English |
|---|---|
| Journal | Receptors and Channels |
| Volume | 5 |
| Issue number | 3-4 |
| Pages (from-to) | 175-83 |
| Number of pages | 9 |
| ISSN | 1060-6823 |
| Publication status | Published - 1997 |
Keywords
- Animals
- Antineoplastic Agents, Phytogenic
- Chloroquine
- Daunorubicin
- Drug Resistance, Multiple
- Mice
- P-Glycoprotein
- Tumor Cells, Cultured
- Verapamil
- Vinblastine