Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0262471 (ENT)
 5,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Large doses of aspirin produce reversible hearing loss and tinnitus. These effects have been attributed to the salicylate ion, the active component of aspirin. Salicylate acts as a competitive antagonist at the anion-binding site of prestin, the motor protein of sensory outer hair cells. This provides an explanation for the hearing loss induced by aspirin. However, the molecular mechanism of salicylate-induced tinnitus remains obscure. One physiological explanation is that salicylate ototoxicity is likely to originate in an alteration to arachidonic acid metabolism. Arachidonic acid potentiates NMDA receptor currents. We therefore tested the involvement of cochlear NMDA receptors in the occurrence of tinnitus. Tinnitus was assessed with a behavioural test based on an active avoidance paradigm. Results showed that the tinnitus induced by salicylate may be suppressed by the introduction of NMDA antagonists into the cochlear fluids. To determine if the activation of NMDA receptors was linked to cyclooxygenase inhibition, we investigated the effect of mefenamate (a potent cyclooxygenase inhibitor). Since NMDA antagonists also blocked mefenamate-induced tinnitus, we suggest that salicylate-induced tinnitus is mediated by cochlear NMDA receptors through the inhibition of cyclooxygenase activity. Target cochlear NMDA receptors may therefore present a therapeutic strategy for the treatment of tinnitus.
B-ENT 2007
PMID:Cochlear NMDA receptor blockade prevents salicylate-induced tinnitus. 1822 4

Electrically evoked otoacoustic emissions are sounds emitted from the inner ear when alternating current is injected into the cochlea. Their temporal structure consists of short- and long-delay components and they have been attributed to the motile responses of the sensory-motor outer hair cells of the cochlea. The nature of these motile responses is unresolved and may depend on either somatic motility, hair bundle motility, or both. The short-delay component persists after almost complete elimination of outer hair cells. Outer hair cells are thus not the sole generators of electrically evoked otoacoustic emissions. We used prestin knockout mice, in which the motor protein prestin is absent from the lateral walls of outer hair cells, and Tecta(Delta ENT/Delta ENT) mice, in which the tectorial membrane, a structure with which the hair bundles of outer hair cells normally interact, is vestigial and completely detached from the organ of Corti. The amplitudes and delay spectra of electrically evoked otoacoustic emissions from Tecta(Delta ENT/Delta ENT) and Tecta(+/+) mice are very similar. In comparison with prestin(+/+) mice, however, the short-delay component of the emission in prestin(-/-) mice is dramatically reduced and the long-delay component is completely absent. Emissions are completely suppressed in wild-type and Tecta(Delta ENT/Delta ENT) mice at low stimulus levels, when prestin-based motility is blocked by salicylate. We conclude that near threshold, the emissions are generated by prestin-based somatic motility.
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PMID:The role of prestin in the generation of electrically evoked otoacoustic emissions in mice. 1823 80