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• W1499694712 startingPage "2166" @default.
• W1499694712 abstract "The calcium channel blockers verapamil and diltiazem have been shown to reverse multidrug resistance, but the mechanism of action of these agents is still unknown. We measured [3H]verapamil, [3H]desmethoxyverapamil, [3H]diltiazem, and [3H]nitrendipine binding to membrane vesicles made from drug-sensitive (KB-3-1), multidrug-resistant (KB-C4 and KB-V1), and revertant (KB-V1-R2) cells. Membrane vesicles from KB-V1 cells bound 10-20-fold more [3H]verapamil and [3H]diltiazem and about 30-fold more [3H]desmethoxyverapamil than did vesicles from the parental KB-3-1 or revertant KB-V1-R2 cell lines. These drugs reverse the multidrug resistance phenotype by increasing accumulation of drugs in the resistant cells. No difference in binding of [3H]nitrendipine, which did not reverse drug resistance, was observed. The binding of vinblastine, desmethoxyverapamil, and diltiazem to KB-V1 vesicles was specific and saturable and was inhibited by desmethoxyverapamil and quinidine greater than vinblastine and diltiazem much greater than daunomycin. In addition, verapamil and diltiazem inhibited the vinblastine photoaffinity labeling of P170, the protein previously shown to be a marker of multidrug resistance." @default.
• W1499694712 created "2016-06-24" @default.
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• W1499694712 date "1987-02-01" @default.
• W1499694712 modified "2023-10-11" @default.
• W1499694712 title "Certain calcium channel blockers bind specifically to multidrug-resistant human KB carcinoma membrane vesicles and inhibit drug binding to P-glycoprotein." @default.
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• W1499694712 doi "https://doi.org/10.1016/s0021-9258(18)61633-3" @default.
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