RGD Reference Report - Presynaptic control of striatal glutamatergic neurotransmission by adenosine A1-A2A receptor heteromers. - Rat Genome Database

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Presynaptic control of striatal glutamatergic neurotransmission by adenosine A1-A2A receptor heteromers.

Authors: Ciruela, F  Casado, V  Rodrigues, RJ  Lujan, R  Burgueno, J  Canals, M  Borycz, J  Rebola, N  Goldberg, SR  Mallol, J  Cortes, A  Canela, EI  Lopez-Gimenez, JF  Milligan, G  Lluis, C  Cunha, RA  Ferre, S  Franco, R 
Citation: Ciruela F, etal., J Neurosci. 2006 Feb 15;26(7):2080-7.
RGD ID: 1625231
Pubmed: PMID:16481441   (View Abstract at PubMed)
PMCID: PMC6674939   (View Article at PubMed Central)
DOI: DOI:10.1523/JNEUROSCI.3574-05.2006   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of glutamate secretion  IDA 1625231K+-evoked glutamate releaseRGD 
negative regulation of synaptic transmission, glutamatergic  IDA 1625231K+-evoked glutamate releaseRGD 
positive regulation of glutamate secretion  IDA 1625231K+-evoked glutamate releaseRGD 
positive regulation of synaptic transmission, glutamatergic  IDA 1625231K+-evoked glutamate releaseRGD 
response to caffeine  IDA 1625231 RGD 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
asymmetric synapse  IDA 1625231; 1625231 RGD 
axolemma  IDA 1625231; 1625231 RGD 
postsynaptic membrane  IDA 1625231; 1625231 RGD 
presynaptic active zone  IDA 1625231; 1625231 RGD 
presynaptic membrane  IDA 1625231; 1625231 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein-containing complex binding  IPIAdora2a (Rattus norvegicus)1625231heterodimerizationRGD 
protein-containing complex binding  IPIAdora1 (Rattus norvegicus)1625231heterodimerizationRGD 

Objects Annotated

Genes (Rattus norvegicus)
Adora1  (adenosine A1 receptor)
Adora2a  (adenosine A2a receptor)


Additional Information