RGD Reference Report - betagamma Dimers mediate synergy of dopamine D2 and adenosine A2 receptor-stimulated PKA signaling and regulate ethanol consumption. - Rat Genome Database

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betagamma Dimers mediate synergy of dopamine D2 and adenosine A2 receptor-stimulated PKA signaling and regulate ethanol consumption.

Authors: Yao, L  Arolfo, MP  Dohrman, DP  Jiang, Z  Fan, P  Fuchs, S  Janak, PH  Gordon, AS  Diamond, I 
Citation: Yao L, etal., Cell. 2002 Jun 14;109(6):733-43.
RGD ID: 1580677
Pubmed: PMID:12086672   (View Abstract at PubMed)

Dopamine release is activated by ethanol and addicting drugs, but molecular mechanisms linking dopaminergic signaling to neuronal responses and drinking behavior are poorly understood. We report that dopamine-D2 receptors induce PKA Calpha translocation and increase CRE-regulated gene expression. Ethanol also activates PKA signaling. Subthreshold concentrations of the D2 agonist NPA and ethanol, without effect alone, together cause synergistic PKA translocation and CRE-mediated gene transcription. D2 or adenosine A2 receptor blockade, pertussis toxin, Rp-cAMPS, or overexpression of dominant-negative peptides that sequester betagamma dimers prevent synergy. Importantly, overexpression of a betagamma inhibitor peptide in the nucleus accumbens strikingly reduces sustained alcohol consumption. We propose that synergy of D2 and A2 confers ethanol hypersensitivity and that betagamma dimers are required for voluntary drinking.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Drd2Ratactivation of protein kinase activity  IDA  RGD 
Drd2Ratadenylate cyclase-modulating G protein-coupled receptor signaling pathway  IDA  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Drd2Ratincreased alcohol consumption  IDA  RGD 
Objects Annotated

Genes (Rattus norvegicus)
Drd2  (dopamine receptor D2)

Objects referenced in this article
Gene Prkaca protein kinase cAMP-activated catalytic subunit alpha Rattus norvegicus

Additional Information