Different synaptic and subsynaptic localization of adenosine A2A receptors in the hippocampus and striatum of the rat
Section snippets
Experimental procedures
Male Wistar rats (6–8 weeks old, 140–160 g; obtained from Harlan Ibérica, Barcelona, Spain) were used throughout this study. All experiments were carried out according to the local guidelines on the ethical use of experimental animals, based on the EU guidelines for use of experimental animals (86/609/EEC), with care to minimize the number of animals used and their suffering, the rats being anesthetized under halothane atmosphere before being killed by decapitation.
Different subcellular localization of A2A receptors in the striatum and hippocampus
To investigate the synaptic localization of striatal and extra-striatal A2A receptors, we started to test if there was an enrichment of A2A receptors in nerve terminals in either the hippocampus or striatum. Thus, we compared the binding density of the selective A2A receptor antagonist, [3H]SCH 58261, in total membranes from the striatum and hippocampus and in membranes of synaptosomes, the best purified model to study presynaptic mechanisms (e.g. Cunha, 1998). We first confirmed that the
Discussion
The main conclusion of the present study is that adenosine A2A receptors have a different subcellular and subsynaptic distribution in the striatum and in the hippocampus. In fact, A2A receptors are more abundantly located outside the active zone in the striatum and the less abundant synaptic A2A receptors in the striatum are mainly located in the postsynaptic density. In contrast, hippocampal A2A receptors are mostly located in nerve terminals and particularly in the presynaptic active zone.
Acknowledgments
We thank to P. C. Pinheiro and J. O. Malva for their participation in preparing and characterizing the subsynaptic fractions, to L. O. Porciúncula for providing some of the cultured hippocampal neurons, to G. Baltazar for her assistance in obtaining cultured striatal neurons and to E. Ongini (Schering-Plough, Milan) for the generous gift of [3H]SCH 58261. This work was supported by Fundação para a Ciência e Tecnologia (POCTI/44740/2002).
References (51)
- et al.
Effect of free radicals on adenosine A2A and dopamine D2 receptors in the striatum of young and aged rats
Neurochem Int
(2004) - et al.
Purinergic P2 receptors trigger adenosine release leading to adenosine A2A receptor activation and facilitation of long-term potentiation in rat hippocampal slices
Neuroscience
(2003) - et al.
The adenosine A2A receptor interacts with the actin-binding protein α-actinin
J Biol Chem
(2003) - et al.
Adenosine A2A receptor antagonism increases striatal glutamate outflow in dopamine-denervated rats
Eur J Pharmacol
(2003) On slices, synaptosomes and dissociated neurones to study in vitro ageing physiology
Trends Neurosci
(1998)Adenosine as a neuromodulator and as a homeostatic regulator in the nervous systemdifferent roles, different sources and different receptors
Neurochem Int
(2001)- et al.
Purinergic modulation of [3H]GABA release from rat hippocampal nerve terminals
Neuropharmacology
(2000) - et al.
Inactivation of adenosine A2A receptor impairs long term potentiation in the accumbens nucleus without altering basal synaptic transmission
Neuroscience
(2001) - et al.
Brain maturation of high-affinity adenosine A2 receptors and their coupling to G-proteins
Dev Brain Res
(1996) - et al.
Further characterization of the binding of the adenosine receptor agonist [3H]CGS 21680 to rat brain using autoradiography
Neuropharmacology
(1995)
Adenosine A2 receptor mediation of pre- and postsynaptic excitatory effects of adenosine in rat hippocampus in vitro
Eur J Pharmacol
Adenosine A2A receptor facilitation of hippocampal synaptic transmission is dependent on tonic A1 receptor inhibition
Neuroscience
Sensitivity to selective adenosine A1 and A2A receptor antagonists of the release of glutamate induced by ischemia in rat cerebrocortical slices
Neuropharmacology
The selective A2A receptor antagonist SCH 58261 reduces striatal transmitter outflow, turning behavior and ischemic brain damage induced by permanent focal ischemia in the rat
Brain Res
Solubilization and immunological identification of presynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors in the rat hippocampus
Neurosci Lett
Transducing system operated by adenosine A2A receptors to facilitate acetylcholine release in the rat hippocampus
Eur J Pharmacol
Subcellular localization of adenosine A1 receptors in nerve terminals and synapses of the rat hippocampus
Brain Res
Synapses in the hippocampus occupy only 1–2% of cell membranes and are spaced less than half-micron aparta quantitative ultrastructural analysis with discussion of physiological implications
Neuropharmacology
Distribution, biochemistry and function of striatal adenosine A2A receptors
Prog Neurobiol
Dimerizationan emerging concept for G protein-coupled receptor ontogeny and function
Annu Rev Pharmacol Toxicol
Enhanced neuronal damage by co-administration of quinolinic acid and free radicals, and protection by adenosine A2A receptor antagonists
Br J Pharmacol
Homodimerization of adenosine A2A receptorsqualitative and quantitative assessment by fluorescence and bioluminescence energy transfer
J Neurochem
A2A adenosine receptor deficiency attenuates brain injury induced by transient focal ischemia in mice
J Neurosci
Role of adenosine and its receptors in the vasodilatation induced in the cerebral cortex of the rat by systemic hypoxia
J Physiol
Age-dependent decrease in adenosine A1 receptor binding sites in the rat braineffect of cis-unsaturated free fatty acids
Eur J Biochem
Cited by (169)
The role of adenosine A<inf>2A</inf> receptors in Alzheimer's disease and tauopathies
2023, NeuropharmacologyA<inf>2A</inf>R and traumatic brain injury
2023, International Review of NeurobiologyAdenosine A<inf>2A</inf>-cannabinoid CB<inf>1</inf> receptor heteromers in the brain: From trans-inhibition to trans-activation
2023, Neurobiology and Physiology of the Endocannabinoid System