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Hear Res. 2010 Sep 1;268(1-2):250-9. doi: 10.1016/j.heares.2010.06.008. Epub 2010 Jun 16.

Competitive antagonism of fluorescent gentamicin uptake in the cochlea.

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  • 1Oregon Hearing Research Center, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.

Abstract

Aminoglycosides enter inner ear hair cells via apical endocytosis, or mechanoelectrical transduction channels, implying that, in vivo, aminoglycosides enter hair cells from endolymph prior to exerting their cytotoxic effect. If so, circulating aminoglycosides likely cross the strial blood-labyrinth barrier and enter marginal cells prior to clearance into endolymph. We characterized the competitive antagonism of unconjugated aminoglycosides on the uptake of fluorescent gentamicin (GTTR) in the stria vascularis and kidney cells at an early time point. In mice, uptake of GTTR by kidney proximal tubule cells was competitively antagonized by gentamicin at all doses, but only weakly by kanamycin (mimicking in vitro data). GTTR fluorescence was approximately 100-fold greater in proximal tubule cells than in the stria vascularis. Furthermore, only high molar ratios of aminoglycosides significantly reduced strial uptake of GTTR. Thus, gentamicin antagonism of GTTR uptake is more efficacious in proximal tubules than in the stria vascularis. Competitive antagonism of GTTR uptake is indicative of specific cell-regulatable uptake mechanisms (e.g., ion channels, transporters) in the kidney. Strial uptake mechanisms have lower specific affinity for gentamicin, and/or density (compared to the kidney), yet may be critical to transport gentamicin across the strial blood-labyrinth barrier into marginal cells.

Copyright (c) 2010 Elsevier B.V. All rights reserved.

PMID:
20561573
[PubMed - indexed for MEDLINE]
PMCID:
PMC2923250
Free PMC Article

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