Post exposure administration of A(1) adenosine receptor agonists attenuates noise-induced hearing loss.

Abstract

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(1) 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 Cl-IB-MECA) were applied to the round window membrane of the cochlea 6h after noise exposure. Auditory brainstem responses measured 48h after drug administration demonstrated partial recovery of hearing thresholds (up to 20dB) 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 Cl-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(1) adenosine receptors as attractive targets for pharmacological interventions to reduce noise-induced cochlear injury after exposure.

• Authors: Ann Chi Yan Wong, Cindy X Guo, Rita Gupta, Gary D Housley, Peter R Thorne, Srdjan M Vlajkovic
• Journal: Hearing research (Hear Res) Vol. 260 Issue 1-2 Pg. 81-8 (Feb 2010) ISSN: 1878-5891 [Electronic] Netherlands
• PMID: 19995597 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2009 Elsevier B.V. All rights reserved.

Chemical References

• Adenosine A1 Receptor Agonists
• Phenethylamines
• Receptor, Adenosine A1
• 2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine
• 3-nitrotyrosine
• 2-chloro-N(6)cyclopentyladenosine
• Tyrosine
• Adenosine
• 2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide

Topics

• Acoustic Stimulation
• Adenosine (analogs & derivatives, metabolism, pharmacology)
• Adenosine A1 Receptor Agonists
• Animals
• Auditory Threshold (drug effects)
• Cochlea (drug effects, metabolism, physiopathology)
• Cochlear Microphonic Potentials (drug effects)
• Disease Models, Animal
• Evoked Potentials, Auditory, Brain Stem (drug effects)
• Hearing Loss, Noise-Induced (metabolism, physiopathology, prevention & control)
• Male
• Oxidative Stress (drug effects)
• Phenethylamines (pharmacology)
• Rats
• Rats, Wistar
• Receptor, Adenosine A1 (metabolism)
• Time Factors
• Tyrosine (analogs & derivatives, metabolism)