Source:http://linkedlifedata.com/resource/pubmed/id/16481441
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
7
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pubmed:dateCreated |
2006-2-16
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pubmed:abstractText |
The functional role of heteromers of G-protein-coupled receptors is a matter of debate. In the present study, we demonstrate that heteromerization of adenosine A1 receptors (A1Rs) and A2A receptors (A2ARs) allows adenosine to exert a fine-tuning modulation of glutamatergic neurotransmission. By means of coimmunoprecipitation, bioluminescence and time-resolved fluorescence resonance energy transfer techniques, we showed the existence of A1R-A2AR heteromers in the cell surface of cotransfected cells. Immunogold detection and coimmunoprecipitation experiments indicated that A1R and A2AR are colocalized in the same striatal glutamatergic nerve terminals. Radioligand-binding experiments in cotransfected cells and rat striatum showed that a main biochemical characteristic of the A1R-A2AR heteromer is the ability of A2AR activation to reduce the affinity of the A1R for agonists. This provides a switch mechanism by which low and high concentrations of adenosine inhibit and stimulate, respectively, glutamate release. Furthermore, it is also shown that A1R-A2AR heteromers constitute a unique target for caffeine and that chronic caffeine treatment leads to modifications in the function of the A1R-A2AR heteromer that could underlie the strong tolerance to the psychomotor effects of caffeine.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1529-2401
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pubmed:author |
pubmed-author:BoryczJanuszJ,
pubmed-author:BurgueñoJavierJ,
pubmed-author:CanalsMeritxellM,
pubmed-author:CanelaEnric IEI,
pubmed-author:CasadóVicentV,
pubmed-author:CiruelaFranciscoF,
pubmed-author:CortésAntonioA,
pubmed-author:CunhaRodrigo ARA,
pubmed-author:FerréSergiS,
pubmed-author:FrancoRafaelR,
pubmed-author:GoldbergSteven RSR,
pubmed-author:López-GiménezJuan FJF,
pubmed-author:LluisCarmeC,
pubmed-author:LujánRafaelR,
pubmed-author:MallolJosefaJ,
pubmed-author:MilliganGraemeG,
pubmed-author:RebolaNelsonN,
pubmed-author:RodriguesRicardo JRJ
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
26
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2080-7
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:16481441-Animals,
pubmed-meshheading:16481441-Caffeine,
pubmed-meshheading:16481441-Cell Line,
pubmed-meshheading:16481441-Corpus Striatum,
pubmed-meshheading:16481441-Dimerization,
pubmed-meshheading:16481441-Humans,
pubmed-meshheading:16481441-Male,
pubmed-meshheading:16481441-Presynaptic Terminals,
pubmed-meshheading:16481441-Rats,
pubmed-meshheading:16481441-Rats, Sprague-Dawley,
pubmed-meshheading:16481441-Receptor, Adenosine A1,
pubmed-meshheading:16481441-Receptors, Adenosine A2,
pubmed-meshheading:16481441-Recombinant Proteins,
pubmed-meshheading:16481441-Synaptic Transmission,
pubmed-meshheading:16481441-Transfection
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pubmed:year |
2006
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pubmed:articleTitle |
Presynaptic control of striatal glutamatergic neurotransmission by adenosine A1-A2A receptor heteromers.
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pubmed:affiliation |
Department of Biochemistry and Molecular Biology, University of Barcelona, 08028 Barcelona, Spain.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Intramural
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