Adenosine and the Auditory System

Abstract

Adenosine is a signalling molecule that modulates cellular activity in the central nervous system and peripheral organs via four G protein-coupled receptors designated A1, A2A, A2B, and A3. This review surveys the literature on the role of adenosine in auditory function, particularly cochlear function and its protection from oxidative stress. The specific tissue distribution of adenosine receptors in the mammalian cochlea implicates adenosine signalling in sensory transduction and auditory neurotransmission although functional studies have demonstrated that adenosine stimulates cochlear blood flow, but does not alter the resting and sound-evoked auditory potentials. An interest in a potential otoprotective role for adenosine has recently evolved, fuelled by the capacity of A1 adenosine receptors to prevent cochlear injury caused by acoustic trauma and ototoxic drugs. The balance between A1 and A2A receptors is conceived as critical for cochlear response to oxidative stress, which is an underlying mechanism of the most common inner ear pathologies (e.g. noise-induced and age-related hearing loss, drug ototoxicity). Enzymes involved in adenosine metabolism, adenosine kinase and adenosine deaminase, are also emerging as attractive targets for controlling oxidative stress in the cochlea. Other possible targets include ectonucleotidases that generate adenosine from extracellular ATP, and nucleoside transporters, which regulate adenosine concentrations on both sides of the plasma membrane. Developments of selective adenosine receptor agonists and antagonists that can cross the blood-cochlea barrier are bolstering efforts to develop therapeutic interventions aimed at ameliorating cochlear injury. Manipulations of the adenosine signalling system thus hold significant promise in the therapeutic management of oxidative stress in the cochlea.

Effects of mitochondrial mutations on hearing and cochlear pathology with age

“…There is a growing body of evidence suggesting that cellular damage from traumatic noise exposure is a result of ROS generation in cochlear sensory cells Bielefeld et al, 2005;Le Prell et al, 2007;Lin et al, 2009;Vlajkovic et al, 2009). Due to the reputed mitochondrial insufficiency in D257A mice, we hypothesized that cochlear cells would fail to be driven by high intensity noise though they have been shown to generate ROS (Trifunovic et al, 2005).…”

Adenosine Kinase: Exploitation for Therapeutic Gain

“…An otoprotective role of adenosine is supported by findings showing that A 1 R activation can prevent cochlear injury caused by acoustic trauma or by ototoxic drugs (Vlajkovic et al, 2009). Therefore, adenosine metabolic enzymes, such as ADK, have emerged as attractive targets for controlling oxidative stress in the cochlea (Vlajkovic et al, 2009). In the adult cochlea of the rat, ADK immunoreactivity was mostly localized to the nuclear or perinuclear region of spiral ganglion neurons, to lateral wall tissue, and to epithelial cells lining the scala media (Vlajkovic et al, 2010).…”

“…Cochlea. Adenosine plays important roles in the auditory system, in particular in protecting the cochlea from oxidative stress (Vlajkovic et al, 2009). An otoprotective role of adenosine is supported by findings showing that A 1 R activation can prevent cochlear injury caused by acoustic trauma or by ototoxic drugs (Vlajkovic et al, 2009).…”

“…Adenosine plays important roles in the auditory system, in particular in protecting the cochlea from oxidative stress (Vlajkovic et al, 2009). An otoprotective role of adenosine is supported by findings showing that A 1 R activation can prevent cochlear injury caused by acoustic trauma or by ototoxic drugs (Vlajkovic et al, 2009). Therefore, adenosine metabolic enzymes, such as ADK, have emerged as attractive targets for controlling oxidative stress in the cochlea (Vlajkovic et al, 2009).…”

The Origins and Early Development of Australasian Auditory Neuroscience

“…Two early graduate students from the University of Auckland, who have gone on to make major contributions to auditory neuroscience are Peter Thorne (who was mentored by Brian Johnstone during his doctoral studies) and Gary Housley (who now heads a major auditory neuroscience research group at the University of NSW). The major foci of research in the Department of Physiology in Auckland are mechanisms of auditory synapse formation and transmission, and of noise-induced cochlear injury (for reviews see [37,38]). …”