RGD Reference Report - Heteromeric association creates a P2Y-like adenosine receptor. - Rat Genome Database
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Heteromeric association creates a P2Y-like adenosine receptor.

Authors: Yoshioka, K  Saitoh, O  Nakata, H 
Citation: Yoshioka K, etal., Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7617-22. Epub 2001 Jun 5.
RGD ID: 8553380
Pubmed: (View Article at PubMed) PMID:11390975
DOI: Full-text: DOI:10.1073/pnas.121587098

Adenosine and its endogenous precursor ATP are main components of the purinergic system that modulates cellular and tissue functions via specific adenosine and ATP receptors (P1 and P2 receptors), respectively. Although adenosine inhibits excitability and ATP functions as an excitatory transmitter in the central nervous system, little is known about the ability of P1 and P2 receptors to form new functional structures such as a heteromer to control the complex purinergic cascade. Here we have shown that G(i/o) protein-coupled A1 adenosine receptor (A1R) and Gq protein-coupled P2Y1 receptor (P2Y1R) coimmunoprecipitate in cotransfected HEK293T cells, suggesting the oligomeric association between distinct G protein-coupled P1 and P2 receptors. A1R and P2Y2 receptor, but not A1R and dopamine D2 receptor, also were found to coimmunoprecipitate in cotransfected cells. A1R agonist and antagonist binding to cell membranes were reduced by coexpression of A1R and P2Y1R, whereas a potent P2Y1R agonist adenosine 5'-O-(2-thiotriphosphate) (ADPbetaS) revealed a significant potency to A1R binding only in the cotransfected cell membranes. Moreover, the A1R/P2Y1R coexpressed cells showed an ADPbetaS-dependent reduction of forskolin-evoked cAMP accumulation that was sensitive to pertussis toxin and A1R antagonist, indicating that ADPbetaS binds A1R and inhibits adenylyl cyclase activity via G(i/o) proteins. Also, a high degree of A1R and P2Y1R colocalization was demonstrated in cotransfected cells by double immunofluorescence experiments with confocal laser microscopy. These results suggest that oligomeric association of A1R with P2Y1R generates A1R with P2Y1R-like agonistic pharmacology and provides a molecular mechanism for an increased diversity of purine signaling.

Annotation

Gene Ontology Annotations    

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Adora1  (adenosine A1 receptor)
P2ry1  (purinergic receptor P2Y1)
P2ry2  (purinergic receptor P2Y2)


Additional Information