A new aspect of aminoglycoside ototoxicity: impairment of cochlear dopamine release.
Aminoglycoside ototoxicity is a well-documented process via several pathophysiological pathways. The protective role of cochlear dopamine, released from the lateral olivocochlear efferents, was implicated previously in case of ischemia or acoustic trauma, as it postsynaptically inhibits the effect of excessively released glutamate from the hair cells. In our in vitro superfusion experiments we showed that neomycin dose- dependently inhibits the dopamine release from isolated guinea pig cochlea, while gentamicin and kanamycin was ineffective on it. After chronic application of neomycin the dopamine outflow did not change significantly, suggesting an adaptive process. In our experiments we have found a possibly new action site of one of the aminoglycoside antibiotics, neomycin.
Gáborján
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Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, P.O. Box 67, H-1450 Budapest, Hungary.
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Répássy
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Vizi
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D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D003051:Cochlea / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004558:Electric Stimulation; D006168:Guinea Pigs; D008297:Male; D009355:Neomycin / Q000633:toxicity; D009498:Neurotoxins / Q000633:toxicity*; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism; D014316:Tritium / Q000493:pharmacokinetics
D000900:Anti-Bacterial Agents; D009498:Neurotoxins; D014316:Tritium; D009355:Neomycin; D004298:Dopamine