Abstract:
Adenosine is a signalling molecule with a role in cytoprotection in many tissues. Previous studies from our group have suggested that A1 adenosine receptor agonists have great potential to ameliorate noise-induced cochlear injury. Current study was undertaken to determine if stimulating A3 adenosine receptors also mitigates hearing loss caused by oxidative stress and promotes cochlear recovery from acoustic trauma. Selective A3 adenosine receptor agonist Cl-IB-MECA (10μM), selective A3 receptor antagonist MRS1191 (100μM) and a control vehicle (1% DMSO) solution have been applied to the round window membrane of the rat cochlea 4-6 hours after exposure to 110dB sound pressure level (SPL) half-octave band noise (8-12 kHz) for 24 hours. The auditory brainstem responses (ABRs) measured 48 hours after drug administration demonstrated no recovery of hearing thresholds in cochleae treated with Cl-IB-MECA or MRS1191. The generation of reactive nitrogen species (RNS) in the cochleae exposed to noise was not altered by administration of Cl-IB-MECA or MRS1191. Stimulating or inhibiting A3 receptor also showed no effect on hair cell survival two days after noise exposure. However, the level of apoptosis in noise exposed cochlea was significantly reduced by CL-IB-MECA. Surprisingly, MRS1191 also reduced apoptosis, although to a lower extent. This suggests that the inhibition of the A3 receptors activates other anti-apoptotic mechanisms, e.g. mediated by A1 adenosine receptors. This study is, therefore, not conclusive regarding the role of A3 adenosine receptors in cochlear protection from noise-induced hearing loss (NIHL). Possible long-term consequences of A3 receptor activation on hearing thresholds and hair cell survival in the noise-exposed cochlea require further investigation.