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A marked increase in cellular ATP consumption was induced by verapamil in the multidrug-resistant (MDR) cell line 2780AD, but not in the drug-sensitive parental cell line A2780. A group of structurally unrelated drugs in concentrations known to reverse MDR, but not the verapamil analog tiapamil, a weak modulator of MDR, had similar effects. This effect was saturated at verapamil concentrations of about 1 microM. These data demonstrate that verapamil concentrations in MDR cells are maintained at a low level at the expense of ATP hydrolysis, and provide a first indication of the amount of metabolic energy used in this process.
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