Lack of cisplatin-ranitidine kinetic interactions: In vivo study in children, and in vitro study using dog renal brush border membrane vesicles

The effect of gentamicin on transport of pyroglutamylhistidine (pGlu-His) was examined in rabbit renal brush-border membrane vesicles (BBMV). Gentamicin, an aminoglycoside antibiotic, is limited in its usage because of nephrotoxicity characterized in part by transport defects in the proximal tubule. Since there is no information regarding the effects of gentamicin on renal peptide carriers, uptake of [3H]pGlu-His was measured in BBMV following either in vivo or in vitro exposure to the antibiotic. One hour after in vivo administration, the maximal rate (Vmax) for pGlu-His transport was significantly reduced in isolated membrane vesicles washed free of the drug, but the apparent Michaelis constant (Km) was unaltered. Coincubation of membranes with gentamicin during measurements of pGlu-His uptake had a similar effect, causing a significant decrease in the Vmax but not the Km of transport. The addition of 5 mM magnesium to the uptake medium prevented the in vitro but not the in vivo effect. The data indicate that high doses of gentamicin inhibit the capacity but not the affinity of dipeptide transport in the kidney, prior to morphological changes which typify acute tubular necrosis. The in vitro effect is rapid and involves a direct action of gentamicin on the brush-border membrane. The in vivo experiments show that toxicity may be prolonged and remains following removal of the drug from the renal brush border.

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In vitro effect of ethanol on sodium and glucose transport in rabbit renal brush border membrane vesicles

Biochimica et Biophysica Acta (BBA) - Biomembranes ◽

10.1016/0005-2736(91)90150-7 ◽

1991 ◽

Vol 1070 (1) ◽

pp. 92-98 ◽

Cited By ~ 13

Author(s):

Paolo Parenti ◽

Barbara Giordana ◽

Giorgio M. Hanozet

Keyword(s):

Glucose Transport ◽

Brush Border ◽

Brush Border Membrane ◽

Membrane Vesicles ◽

Brush Border Membrane Vesicles ◽

Renal Brush Border Membrane ◽

Vitro Effect ◽

Renal Brush Border

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Low-affinity transport of pyroglutamyl-histidine in renal brush-border membrane vesicles

AJP Cell Physiology ◽

10.1152/ajpcell.1989.257.5.c971 ◽

1989 ◽

Vol 257 (5) ◽

pp. C971-C975 ◽

Cited By ~ 3

Author(s):

H. A. Skopicki ◽

K. Fisher ◽

D. Zikos ◽

G. Flouret ◽

D. R. Peterson

Keyword(s):

Brush Border ◽

Brush Border Membrane ◽

Membrane Vesicles ◽

Brush Border Membrane Vesicles ◽

Proximal Tubular Cells ◽

Tubular Cells ◽

Luminal Membrane ◽

Renal Brush Border Membrane ◽

Proximal Tubular ◽

Renal Brush Border

These studies were performed to determine if a low-affinity carrier is present in the luminal membrane of proximal tubular cells for the transport of the dipeptide, pyroglutamyl-histidine (pGlu-His). We have previously described the existence of a specific, high-affinity, low-capacity [transport constant (Kt) = 9.3 X 10(-8) M, Vmax = 6.1 X 10(-12) mol.mg-1.min-1] carrier for pGlu-His in renal brush-border membrane vesicles. In the present study, we sought to demonstrate that multiple carriers exist for the transport of a single dipeptide by determining whether a low-affinity carrier also exists for the uptake of pGlu-His. Transport of pGlu-His into brush-border membrane vesicles was saturable over the concentration range of 10(-5)-10(-3) M, yielding a Kt of 6.3 X 10(-5) M and a Vmax of 2.2 X 10(-10) mol.mg-1.min-1. Uptake was inhibited by the dipeptides glycyl-proline, glycyl-sarcosine, and carnosine but not by the tripeptide pyroglutamyl-histidyl-prolinamide. We conclude that 1) pGlu-His is transported across the luminal membrane of the proximal tubule by multiple carriers and 2) the lower affinity carrier, unlike the higher affinity carrier, is nonspecific with respect to other dipeptides.

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