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Gentamicin and verapamil compete for a common transport mechanism in renal brush border membrane vesicles [published erratum appears in J Pharmacol Exp Ther 1990 May;253(2):i]

PP Sokol, KR Huiatt, PD Holohan and CR Ross

Department of Pharmacology, State University of New York, Health Science Center, Syracuse.

The effects of gentamicin, an aminoglycoside antibiotic, and verapamil, a calcium channel blocker, on the transport systems in canine renal brush border membrane vesicles were examined. They were tested for their effects on the transport of either a prototypic organic cation, N1-[3H]methylnicotinamide or a prototypic organic anion p- [3H]aminohippurate. They were classified as a substrate for either transport system if the following two criteria were fulfilled: 1) cis inhibition and 2) trans stimulation with concentrative uptake of the prototypic ion. Both gentamicin and verapamil cis inhibited the uptake of the prototypic organic cation N1[3H]methylnicotinamide, with Ki values of 450 and 5 microM, respectively. Similarly, both drugs trans- stimulated N1-methylnicotinamide influx and produced concentrative uptake over the equilibrium value. The results demonstrate that gentamicin and verapamil are substrates for the renal organic cation transport system. We postulate that high-affinity substrates should protect against gentamicin-induced nephrotoxicity.

Volume 251, Issue 3, pp. 937-942, 12/01/1989
Copyright © 1989 by American Society for Pharmacology and Experimental Therapeutics




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