Gentamicin and verapamil compete for a common transport mechanism in renal brush border membrane vesicles.
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.
Sokol
P P
PP
Department of Pharmacology, State University of New York, Health Science Center, Syracuse.
Huiatt
K R
KR
Holohan
P D
PD
Ross
C R
CR
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004285:Dogs; D005839:Gentamicins / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008871:Microvilli / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives / Q000378:metabolism; D014700:Verapamil / Q000493:pharmacokinetics / Q000494:pharmacology*; D010130:p-Aminohippuric Acid / Q000493:pharmacokinetics
D005839:Gentamicins; D009536:Niacinamide; D014700:Verapamil; C024058:N(1)-methylnicotinamide; D010130:p-Aminohippuric Acid