Differential distribution of adenosine receptors in rat cochlea

Abstract

Adenosine is a constitutive cell metabolite that can be released from cells via specific bi-directional transporters and is an end-point for nucleotide hydrolysis. In the extracellular space, adenosine becomes a signalling molecule for P1 (adenosine) receptors that modulate physiological responses in a wide range of mammalian tissues. Whereas adenosine signalling has been implicated in the regulation of cochlear blood flow and in cochlear protection from oxidative damage, the potential roles for adenosine signalling in the modulation of sound transduction and auditory neurotransmission have not been established. We have characterised the expression and distribution of adenosine receptors in the rat cochlea. mRNA transcripts for all four subtypes of adenosine receptors (A(1), A(2A), A(2B) and A(3)) were detected in dissected cochlear tissue by using reverse transcription/polymerase chain reaction analysis. The protein distribution for the A(1), A(2A) and A(3) receptor subtypes was identified by immunoperoxidase histochemistry and confocal immunofluorescence labelling. These receptors were differentially expressed in the organ of Corti, spiral ganglion neurones, lateral wall tissues and cochlear blood vessels. The distribution of adenosine receptors in sensory and neural tissues and in the vasculature coincided with other elements of purinergic signalling (P2X and P2Y receptors, ectonucleotidases), consistent with the integrative regulation of many physiological processes in the cochlea by extracellular nucleotides and nucleosides. Our study provides a framework for further investigation of adenosine signalling in the inner ear, including putative roles in oxidative stress responses.

Purinergic signaling in the inner ear

“…Further, the expression level of A 1 and A 3 receptors was found to be higher in the well-vascularized cochlear lateral wall and organ of Corti than in the eighth nerve of chinchilla cochlea (Ford et al, 1997). Recently, mRNA transcripts for all four subtypes of adenosine receptors were detected in rat cochlear tissue, and adenosine receptors were found to be differentially expressed in the sensory hair cells and supporting cells of the organ of Corti, spiral ganglion neurons, and cochlear vasculature (Vlajkovic et al, 2007) Several studies have indicated the presence in cochlear tissues of adenosine receptors that are thought to be activated through generation of reactive oxygen species (ROS) in response to various stresses to the inner ear. Noise exposure induced A 1 receptor expression, which might be mediated, in part, through generation of ROS and activation of nuclear factor (NF)-kB (Ramkumar et al, 2004).…”

Purinergic signaling in cochleovestibular hair cells and afferent neurons

“…An immunohistochemical study showed expression of three subtypes of P1 adenosine receptors (A 1 R, A 2A R, and A 3 R) in both IHCs and SGNs of adult rats [41], but develop- To date, there is little evidence of functional P1 receptors in the inner ear. In the cochlear partition, perfusion of adenosine in either perilymph or endolymph showed no changes in cochlear physiological parameters such as CAP [23,25] and no in vitro study has been published.…”

Differential expression of P2Y receptors in the rat cochlea during development

“…While there has been an extensive analysis of P2X receptor expression both in the developing and mature cochlea across several species (for reviews, see [1,22]), and adenosine receptor and ecto-nucleotidase activity has been established [23][24][25]. The sites and mechanisms of action of P2Y receptor activity in the cochlea are still emerging.…”