Abstract
Adenosine receptors (ARs) comprise a group of G protein-coupled receptors (GPCR) which mediate the physiological actions of adenosine. To date, four AR subtypes have been cloned and identified in different tissues. These receptors have distinct localization, signal transduction pathways and different means of regulation upon exposure to agonists. This review will describe the biochemical characteristics and signaling cascade associated with each receptor and provide insight into how these receptors are regulated in response to agonists. A key property of some of these receptors is their ability to serve as sensors of cellular oxidative stress, which is transmitted by transcription factors, such as nuclear factor (NF)-κB, to regulate the expression of ARs. Recent observations of oligomerization of these receptors into homo- and heterodimers will be discussed. In addition, the importance of these receptors in the regulation of normal and pathological processes such as sleep, the development of cancers and in protection against hearing loss will be examined.
Highlights
Adenosine is produced primarily from the metabolism of adenosine triphosphate (ATP) and exerts pleiotropic functions throughout the body
These receptors are highly localized to presynaptic regions, where they modulate the release of neurotransmitters such as glutamate, acetylcholine, GABA and noradrenaline [32,33,34,35]
Coelho et al [54] reported that hypoxia decreases the density of A1AR in rat hippocampal slices. This desensitization could be mimicked by 2-chloroadenosine (CADO), and was prevented by adding the A1AR antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). These results suggest that hypoxia leads to an increase in extracellular adenosine levels, and a subsequent, quite rapid (
Summary
Adenosine is produced primarily from the metabolism of adenosine triphosphate (ATP) and exerts pleiotropic functions throughout the body. In the CNS, A1ARs are widely distributed on neurons in the cortex, hippocampus and cerebellum [5] These receptors are present on astrocytes [26], oligodendrocytes [27] and microglia [28]. A2AAR have a more restrictive localization in the striatum and olfactory bulb [5] These receptors are present in neurons, microglia and oligodendrocytes and possibly astrocytes [29,30]. The presence of A2AAR has been described in dendritic spines and postsynaptic regions of the basal ganglia [31] These receptors are highly localized to presynaptic regions (in hippocampus), where they modulate the release of neurotransmitters such as glutamate, acetylcholine, GABA and noradrenaline [32,33,34,35]. Low levels of the A3AR are detectable in the hippocampus, cortex, cerebellum and striatum [5], with cellular localization in neurons, astrocytes and microgila [38,39,40]
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