Role of adenosine receptors in auditory functions

Following the initial characterization of adenosine receptors in the cochlea, it was shown that activation of these receptors increased the activity of antioxidant enzymes in the cochlea. The cochlea also expresses various ATP hydrolytic enzymes responsible for the synthesis of adenosine, along with equilibrative and concentrative transporters. Adenosine receptors show distinct distribution patterns in the cochlea. Their ability to increase antioxidant enzymes, prompted future studies to determine the efficacy of adenosine receptor agonists to treat hearing loss induced by chemotherapeutic agents and noise trauma, conditions linked to the generation of reactive oxygen species. To date, agents that activate the A1 adenosine receptor appear to show efficacy for the treatment of hearing loss in animal studies. It is yet to be shown that these agents are effective for preventing and treating hearing loss in humans. A major problem yet to be addressed is how to administer these drugs for treatment of hearing loss without producing significant side effects.