Elsevier

Progress in Neurobiology

Volume 48, Issue 3, February 1996, Pages 167-189
Progress in Neurobiology

Adenosine A2 receptor-mediated excitatory actions on the nervous system

https://doi.org/10.1016/0301-0082(95)00035-6Get rights and content

Abstract

The distribution, molecular structure and role of adenosine A2 receptors in the nervous system, is reviewed. The adenosine A2a receptor subtype, identified in the nervous system with ligand binding, functional studies or genetic molecular techniques, has been demonstrated in the striatum and other basal ganglia structures, in the hippocampus, in the cerebral cortex, in the nucleus tractus solitarius, in motor nerve terminals, in noradrenergic terminals in the vas deferens, in myenteric neurones of the ileum, in the retina and in the carotid body. The A2b receptors have been identified in glial and neuronal cells, and may have a widespread distribution in the brain. Activation of adenosine A2a receptors can enhance the release of several neurotransmitters, such as acetylcholine, glutamate, and noradrenaline. The release of GABA might be either enhanced or inhibited by A2a receptor activation. The A2 receptor activation also modulates neuronal excitability, synaptic plasticity, as well as locomotor activity and behaviour. The ability of A2 receptors to interact with other receptors for neurotransmitters/neuromodulators, such as dopamine D2 and D1 receptors, adenosine A1 receptors, CGRP receptors, metabotropic glutamate receptors and nicotinic autofacilitatory receptors, expands the range of possibilities used by adenosine to interfere with neuronal function and communication. These A2 receptor-mediated adenosine actions might have potential therapeutic interest, in particular in movement disorders such as Parkinson's disease and Huntington's chorea, as well as in schizophrenia, Alzheimer's disease, myasthenia gravis and myasthenic syndromes.

References (238)

  • F. Caciagli et al.

    Class II of metabotropic glutamate receptors modulate the evoked release of adenosine and glutamate from rat hippocampal slices

    Pharmacol. Res.

    (1995)
  • P. Canhão et al.

    1,3-Dipropyl-8-cyclopentylxanthine attenuates the NMDA response to hypoxia in the rat hippocampus

    Brain Res.

    (1994)
  • M. Castillo-Meléndez et al.

    Presynaptic adenosine A2a receptors on soma and central terminals of rat vagal afferent neurons

    Brain Res.

    (1994)
  • Y. Chern et al.

    Molecular cloning of a novel adenosine receptor gene from rat brain

    Biochem. Biophys. Res. Commun.

    (1992)
  • P. Correia-de-Sá et al.

    Facilitation of [3H]-ACh release by forskolin depends on A2-adenosine receptor activation

    Neurosci. Letts

    (1993)
  • P. Correia-de-Sá et al.

    Tonic A2a receptor activation modulates nicotinic autoreceptor function at the rat neuromuscular junction

    Eur. J. Pharmacol.

    (1994)
  • R.A. Cunha et al.

    Evidence for functionally important adenosine A2a receptors in the rat hippocampus

    Brain Res.

    (1994)
  • R.A. Cunha et al.

    Adenosine A2a receptors stimulate acetylcholine release from nerve terminals of the rat hippocampus

    Neurosci. Letts

    (1995)
  • J.W. Daly et al.

    Adenosine receptors in the central nervous system: relationship to the central action of methylxanthines

    Life Sci.

    (1981)
  • M.S. Dar

    Functional correlation between subclasses of brain adenosine receptor affinities and ethanol-induced motor incoordination in mice

    Pharmacol. Biochem. Behav.

    (1990)
  • A. de Mendonça et al.

    2-Chloroadenosine decreases long-term potentiation in the hippocampal CA1 area of the rat

    Neurosci. Letts

    (1990)
  • A. de Mendonça et al.

    Endogenous adenosine modulates long-term potentiation in the hippocampus

    Neuroscience

    (1994)
  • M.J. Durcan et al.

    Evidence for adenosine A2 receptor involvement in the hypomobility effects of adenosine analogues in mice

    Eur. J. Pharmacol.

    (1989)
  • S. Ferré et al.

    Dopamine denervation leads to an increase in the membrane interactions between adenosine A2 and dopamine D2 receptors in the neostriatum

    Brain Res.

    (1992)
  • S. Ferré et al.

    Stimulation of adenosine A2 receptors induces catalepsy

    Neurosci. Letts

    (1991)
  • S. Ferré et al.

    Adenosine-dopamine interactions in the brain

    Neuroscience

    (1992)
  • J.S. Fink et al.

    Molecular cloning of the rat A2 adenosine receptor: selective co-expression with D2 dopamine receptors in rat striatum

    Mol. Brain Res.

    (1992)
  • S. Fujii et al.

    Adenosine A2 receptor antagonist facilitates the reversal of long-term potentiation (depotentiation) of evoked postsynaptic potentials but inhibits that of population spikes in hippocampal CA1 neurons

    Neurosci. Letts

    (1992)
  • F. Fujiwara et al.

    Adenosine enhances neuronal damage during deprivation of oxygen and glucose in guinea pig superior collicular slices

    Neurosci. Letts

    (1994)
  • T.J. Furlong et al.

    Molecular characterization of a human brain A2 adenosine receptor

    Mol. Brain Res.

    (1992)
  • A. Gharib et al.

    Evidence for A2b receptors in the rat pineal gland

    Eur. J. Pharmacol.-Mol. Pharmacol. Sec.

    (1992)
  • M. Hawkins et al.

    Effects of chronic administration of caffeine on adenosine A1 and A2 receptors in rat brain

    Brain Res. Bull.

    (1988)
  • H. Hirai et al.

    Adenosine facilitates glutamate release in a protein kinase-dependent manner in the superior colliculus slices

    Eur. J. Pharmacol.

    (1994)
  • A.P. Ijzerman et al.

    Molecular modelling of adenosine receptors. The ligand-binding site on the rat adenosine A2a receptor

    Eur. J. Pharmacol.-Mol. Pharmacol. Sec.

    (1994)
  • A. Ishikawa et al.

    Excitatory effects of adenosine receptor agonists and antagonists on neurotransmission in guinea-pig superior collicular slices

    Neurosci. Letts

    (1994)
  • S. James et al.

    The subcellular distribution of [3H]-CGS21680 binding sites in the rat striatum: copurification with cholinergic nerve terminals

    Neurochem. Int.

    (1993)
  • C.A. Janusz et al.

    The A2-selective adenosine analogue, CGS 21680, depresses locomotor activity but does not block amygdala kindled seizures in rats

    Neurosci. Letts

    (1992)
  • C.A. Janusz et al.

    Adenosinergic modulation of the EEG and locomotor effects of the A2 agonist, CGS 21680

    Pharmacol. Biochem. Behav.

    (1993)
  • M.F. Jarvis et al.

    Direct autoradiographic localization of A2 adenosine receptors in the rat brain using the A2-selective agonist, [3H]CGS 21680

    Eur. J. Pharmacol.

    (1989)
  • X.-D. Ji et al.

    Solubilized rabbit striatal A2a-adenosine receptors: stability and antagonist binding

    Arch. Biochem. Bioph.

    (1993)
  • M.B. Anand-Srivastava et al.

    Regulation of adenosine-sensitive adenylate cyclase from rat brain

    J. Neurochem.

    (1980)
  • R. Askalan et al.

    Role of histidine residues in the adenosine A2a receptor ligand-binding site

    J. Neurochem.

    (1994)
  • R.A. Barraco et al.

    Purinergic receptors in the nucleus tractus solitarius mediate distinct cardiorespiratory response patterns

    Drug Dev. Res.

    (1993)
  • W.W. Barrington et al.

    Identification of the A2 adenosine receptor binding subunit by photoaffinity crosslinking

  • W.W. Barrington et al.

    Glycoprotein nature of the A2-adenosine receptor binding subunit

    Mol. Pharmacol.

    (1990)
  • I. Biaggioni et al.

    Caffeine and theophylline as adenosine receptor antagonists

    J. Pharmacol. Exp. Ther.

    (1991)
  • L.E. Bracket et al.

    Functional characterization of the A2b adenosine receptor in NIH 3T3 fibroblasts

    Biochem. Pharmacol.

    (1994)
  • S. Braun et al.

    Adenosine receptor permanently coupled to turkey erythrocyte adenylate cyclase

    Biochemistry

    (1979)
  • S.J. Brown et al.

    Both A1 and A2a purine receptors regulate striatal acetylcholine release

    J. Neurochem.

    (1990)
  • R.F. Bruns et al.

    Characterization of the A2 adenosine receptor labelled by [3H]NECA in rat striatal membranes

    Mol. Pharmacol.

    (1986)
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