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Adenosine A2A receptors control the extracellular levels of adenosine through modulation of nucleoside transporters activity in the rat hippocampus

dc.contributor.authorDuarte, António Pinto
dc.contributor.authorCoelho, Joana E.
dc.contributor.authorCunha, Rodrigo A.
dc.contributor.authorRibeiro, Joaquim Alexandre
dc.contributor.authorSebastião, Ana M
dc.date.accessioned2013-01-17T16:57:00Z
dc.date.available2013-01-17T16:57:00Z
dc.date.issued2005
dc.description© 2005 International Society for Neurochemistryeng
dc.description.abstractAdenosine, a neuromodulator of the CNS, activates inhibitory- A1 receptors and facilitatory-A2A receptors; its synaptic levels are controlled by the activity of bi-directional equilibrative nucleoside transporters. To study the relationship between the extracellular formation/inactivation of adenosine and the activation of adenosine receptors, we investigated how A1 and A2A receptor activation modifies adenosine transport in hippocampal synaptosomes. The A2A receptor agonist, CGS 21680 (30 nM), facilitated adenosine uptake through a PKCdependent mechanism, but A1 receptor activation had no effect. CGS 21680 (30 nM) also increased depolarization-induced release of adenosine. Both effects were prevented by A2A receptor blockade. A2A receptor-mediated enhancement of adenosine transport system is important for formatting adenosine neuromodulation according to the stimulation frequency, as: (1) A1 receptor antagonist, DPCPX (250 nM), facilitated the evoked release of [3H]acetylcholine under lowfrequency stimulation (2 Hz) from CA3 hippocampal slices, but had no effect under high-frequency stimulation (50 Hz); (2)either nucleoside transporter or A2A receptor blockade revealed the facilitatory effect of DPCPX (250 nM) on [3H]acetylcholine evoked-release triggered by high-frequency stimulation. These results indicate that A2A receptor activation facilitates the activity of nucleoside transporters, which have a preponderant role in modulating the extracellular adenosine levels available to activate A1 receptors.eng
dc.description.sponsorshipWork supported by Fundação para a Ciência e a Tecnologia (FCT). APD and JEC were receiving FCT fellowships (POCTI/37332/FCB/ 2001 and SFRH/BD/937/2000)eng
dc.identifier.citationJournal of Neurochemistry, 2005, 93, 595–604eng
dc.identifier.issn0022-3042
dc.identifier.urihttp://dx.doi.org/10.1111/j.1471-4159.2005.03071.x
dc.identifier.urihttp://hdl.handle.net/10451/7526
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherWiley-Blackwellpor
dc.relation.publisherversionThe definitive version is available at www3.interscience.wiley.comeng
dc.subjectA2A receptorseng
dc.subjectAcetylcholineeng
dc.subjectAdenosineeng
dc.subjectHippocampuseng
dc.subjectNucleoside transporterseng
dc.subjectStimulation frequencyeng
dc.titleAdenosine A2A receptors control the extracellular levels of adenosine through modulation of nucleoside transporters activity in the rat hippocampuseng
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage604por
oaire.citation.startPage595por
oaire.citation.titleJournal of Neurochemistryeng
oaire.citation.volume93por
person.familyNameSebastião
person.givenNameAna M
person.identifier.ciencia-idF112-55E8-E37E
person.identifier.orcid0000-0001-9030-6115
person.identifier.scopus-author-id7004409879
rcaap.rightsrestrictedAccesspor
rcaap.typearticlepor
relation.isAuthorOfPublication304abd7f-071b-4447-a8a3-4aa5f0547141
relation.isAuthorOfPublication.latestForDiscovery304abd7f-071b-4447-a8a3-4aa5f0547141

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