PMID: 9635154Jun 23, 1998Paper

Gentamicin uptake by LLCPK1 cells: effect of intracellular and extracellular pH changes

Canadian Journal of Physiology and Pharmacology
E C Lui, R Bendayan

Abstract

The mechanisms by which aminoglycosides are transported across the luminal membrane of renal proximal tubular cells remain unclear. A luminal organic cation/H+ exchange as well as an adsorptive endocytosis membrane process has been proposed to be involved in gentamicin renal accumulation. The objectives of this work were to explore further the effects of intracellular and extracellular pH changes on gentamicin uptake. [3H]Gentamicin uptake by a continuous renal epithelial cell line, LLCPK1, grown as a monolayer on an impermeable surface was measured at different temperatures and pH conditions and in the presence of various inhibitors. Uptake of gentamicin was found to be carrier mediated (K(m) = 1.26 +/- 0.22 mM, Vmax = 289 +/- 27 pmol.mg-1.min-1), energy dependent (inhibited in part by sodium azide), and temperature dependent (37 degrees C > 4 degrees C). Fifteen-minute gentamicin (10 microM) uptake was inhibited by 1 mM of the organic cations cimetidine (61.0%), quinidine (73.5%), quinine (68.6%), and verapamil (61.5%). More importantly, while an outwardly directed proton gradient did not have a significant effect on gentamicin uptake, extracellular acidification (pH 6.5), which leads to a higher degree of gentamicin ionizati...Continue Reading

Citations

Nov 5, 2016·Annual Review of Physiology·Megan L Eshbach, Ora A Weisz
Jan 10, 2002·Journal of Pharmaceutical Sciences·Patrick Poulin, Frank-Peter Theil

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