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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Receptors and Channels |
| Vol/bind | 5 |
| Udgave nummer | 3-4 |
| Sider (fra-til) | 175-83 |
| Antal sider | 9 |
| ISSN | 1060-6823 |
| Status | Udgivet - 1997 |