Gentamicin inhibits Na+-dependent d-glucose transport in rabbit kidney brush-border membrane vesicles

doi:10.1016/0005-2736(86)90301-9

Biochimica et Biophysica Acta (BBA) - Biomembranes

Volume 858, Issue 1, 13 June 1986, Pages 153-160

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Abstract

We studied the effect of gentamicin on Na⁺-dependent d-glucose transport into brush-border membrane vesicles isolated from rabbit kidney outer cortex (early proximal tubule) and outer medulla (late proximal tubule) in vitro. We found the same osmotically active space and nonspecific binding between control and gentamicin-treated brush-border membrane vesicles. There was no difference in the passive permeability properties between control and gentamicin-treated brush-border membrane vesicles. Kinetic analyses of d-glucose transport into 1 mM gentamicin-treated brush-border membrane vesicles demonstrated that gentamicin decreased V_max in the outer cortical preparation, while it did not affect V_max in the outer medullary preparation. With regard to K_m, there was no effect of gentamicin in any vesicle preparation. When brush-border membrane vesicles were incubated with higher concentrations of gentamicin, Na⁺-dependent d-glucose transport was inhibited dose-dependently in both outer cortical and outer medullary preparations. Dixon plots yield inhibition constant K_i = 4 mM in the outer cortical preparation and K_i = 7 mM in the outer medullary preparation. These results indicate that the Na⁺-dependent d-glucose transport system in early proximal tubule is more vulnerable to gentamicin toxicity than that in late proximal tubule.

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Cited by (14)

Comparative effects of gentamicin and netilmicin on Na<sup>+</sup>-dependent d-glucose transport in rabbit renal brush-border membrane vesicles
1991, Toxicology in Vitro
The effects of gentamicin and netilmicin administration on Na⁺-dependent d-glucose transport in rabbit renal brush-border membrane vesicles (BBMV) were investigated. BBMV were isolated from rabbit kidney outer cortex (early proximal tubule) and outer medulla (late proximal tubule) 60 min after iv drug administration. Pharmacokinetics and renal accumulation of gentamicin and netilmicin were also studied. We found decreased affinity in the Na⁺-dependent d-glucose transport system after gentamicin administration only in the outer cortical preparations and not in the outer medullary ones. Gentamicin administration did not affect the membrane permeability or d-glucose distribution space of BBMV. Netilmicin had no effect on Na⁺-dependent d-glucose transport. The V_max values of Na⁺-dependent d-glucose transport were not affected by either gentamicin or netilmicin administration in both outer cortical and outer medullary preparations. Thus, gentamicin was shown to have stronger effects on Na⁺-dependent d-glucose transport than did netilmicin. This result is consistent with the rank of nephrotoxicity for gentamicin and netilmicin. Furthermore, the Na⁺-dependent d-glucose transport system in the early proximal tubule seems to be more vulnerable to gentamicin toxicity than that in the late proximal tubule. Pharmacokinetic parameters and renal accumulation of gentamicin and netilmicin were not significantly different from each other. Thus, the difference in transport inhibition by gentamicin and netilmicin cannot be accounted for by using pharmacokinetic factors of these two drugs.
Netilmicin affects Na<sup>+</sup>-dependent d-glucose transport and the membrane fluidity of rabbit renal brush-border membrane vesicles: a comparison with gentamicin
1990, Toxicology Letters
Decrease in the fluidity of brush-border membrane vesicles induced by gentamicin a spin-labeling study
1989, Biochemical Pharmacology
In our previous paper (Horio et al., Biochim Biophys Acta858: 153–160, 1986), we reported that the addition of gentamicin in vitro to rabbit renal brush-border membrane vesicles decreases the apparent V_max of Na⁺-dependent d-glucose transport without affecting the apparent K_m. In the present study, we investigated the effects of gentamicin on the physical state of spin-labeled rabbit renal brush-border membranes, using electron spin resonance spectrometry. Brush-border membrane vesicles were prepared from outer cortex (mainly contains early proximal tubule) and outer medulla (containing primarily late proximal tubule), and the gentamicin toxicities in both preparations were compared. Significant decreases were observed in the membrane fluidity of 5 mM gentamicin-treated brush-border membranes. The fluidity of outer cortical brush-border membranes was affected at both 25° and 35°, whereas that of outer medullary membranes was affected only at 35°. Two different stearic acid spin labels revealed that gentamicin affected the fluidity only in the superficial region of the membranes. We also demonstrated that the gentamicin-induced decreases in Na⁺-dependent d-glucose transport and in the membrane fluidity were recovered by washing gentamicin-treated brush-border membranes. We suggest that gentamicin binds to the superficial region of brush-border membranes and inhibits Na⁺ dependent d-glucose transport across brush-border membranes through the decrease in the membrane fluidity.
Inhibition of alkaline phosphatase activity and d-glucose uptake in rat renal brush-border membrane vesicles by aminoglycosides
1987, BBA - Biomembranes
The binding of aminoglycoside antibiotics to, and their effects on, the plasma membrane were studied using isolated rat renal brush-border membrane vesicles. Dibekacin was noted to bind with brush-border membrane vesicles having a single class of many binding sites. ³H-labeled dibekacin binding was inhibited competitively by unlabeled dibekacin, gentamicin or amikacin. The inhibition constants obtained from the Dixon plots followed the order of gentamicin ≅ dibekacin > amikacin. The alkaline phosphatase activity of brush-border membrane vesicles was inhibited by gentamicin significantly, as was also observed by a histochemical study. Sodium-dependent d-glucose uptake by brush-border membrane vesicles was significantly inhibited by the addition of gentamicin.
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Regular paperGentamicin inhibits Na+-dependent d-glucose transport in rabbit kidney brush-border membrane vesicles

Abstract

Am. J. Med.

J. Pediatr.

Kidney Int.

Kidney Int.

Biochim. Biophys. Acta

Biochim. Biophys. Acta

J. Infect. Dis.

Am. J. Pathol.

Lab. Invest.

Am. J. Clin. Pathol.

Regular paper
Gentamicin inhibits Na⁺-dependent d-glucose transport in rabbit kidney brush-border membrane vesicles