This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Warr, J. R. Articles by Fergusson, J. Search for Related Content PubMed PubMed Citation Articles by Warr, J. R. Articles by Fergusson, J.

Properties of Verapamil-hypersensitive Multidrug-resistant Chinese Hamster Ovary Cells¹

Department of Biology, University of York, Heslington, York, YO1 5DD, United Kingdom

Two vincristine resistant Chinese hamster ovary cell lines have been shown previously to be hypersensitive to the calcium channel blocker, verapamil. They are now shown to be hypersensitive to the membraneactive agent quinidine sulfate and to the calcium channel blockers diltiazem and nicardipine. Hypersensitivity to quinidine sulfate implies that calcium channels are not the primary target for these drug effects on these cell lines and is consistent with our previous observation that their calcium accumulation is normal in the presence and absence of verapamil. The two cell lines have elevated levels of membrane P-glycoprotein and of two cytosolic proteins, M_r 27,000 and pI 6.0 and 6.4. Revertants have normal levels of these cytosolic proteins, suggesting that these proteins may play a role in conferring resistance. [³H]Verapamil accumulation by the two cell lines is lower than in controls. One of the cell lines has been hybridized to normal cells and the vincristine resistance and verapamil sensitivity of three hybrid clones has been determined. Vincristine resistance is semidominant but verapamil hypersensitivity is completely recessive.

¹ This work was supported by grants from the Yorkshire Cancer Research Campaign.

² To whom requests for reprints should be addressed.

Received 12/14/87. Revised 4/ 4/88. Accepted 5/ 2/88.

This article has been cited by other articles:

				G. D. Eytan, R. Regev, G. Oren, and Y. G. Assaraf The Role of Passive Transbilayer Drug Movement in Multidrug Resistance and Its Modulation J. Biol. Chem., May 31, 1996; 271(22): 12897 - 12902. [Abstract] [Full Text] [PDF]