Journal
HEARING RESEARCH
Volume 260, Issue 1-2, Pages 81-88Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.heares.2009.12.004
Keywords
Adenosine receptors; Cochlea; Hearing; Noise; Otoprotection
Funding
- Royal National Institute for Deaf People (RNID, UK)
- Deafness Research Foundation (NZ)
- Auckland Medical Research Foundation
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Adenosine is a constitutive cell metabolite with a putative role in protection and regeneration in many tissues. This study was undertaken to determine if adenosine signalling pathways are involved in protection against noise injury. A, adenosine receptor expression levels were altered in the cochlea exposed to loud sound, suggesting their involvement in the development of noise injury. Adenosine and selective adenosine receptor agonists (CCPA, CGS-21680 and CI-IB-MECA) were applied to the round window membrane of the cochlea 6 h after noise exposure. Auditory brainstem responses measured 48 h after drug administration demonstrated partial recovery of hearing thresholds (up to 20 dB) in the cochleae treated with adenosine (non-selective adenosine receptor agonist) or CCPA (selective A(1) adenosine receptor agonist). In contrast, the selective A(2A) adenosine receptor agonist CGS-21680 and A(3) adenosine receptor agonist CI-IB-MECA did not protect the cochlea from hearing loss. Sound-evoked cochlear potentials in control rats exposed to ambient noise were minimally altered by local administration of the adenosine receptor agonists used in the noise study. Free radical generation in the cochlea exposed to noise was reduced by administration of adenosine and CCPA. This study pinpoints A, adenosine receptors as attractive targets for pharmacological interventions to reduce noise-induced cochlear injury after exposure. (C) 2009 Elsevier B.V. All rights reserved.
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