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Journal of Molecular Neuroscience

, Volume 26, Issue 2–3, pp 233–238 | Cite as

Functions of heteromeric association between adenosine and P2Y receptors

  • Hiroyasu Nakata
  • Kazuaki Yoshioka
  • Toshio Kamiya
  • Hirofumi Tsuga
  • Koshi Oyanagi
Short Review

Abstract

It is now well accepted that G protein-coupled receptors (GPCRs) can be directly associated, as either homo-or hetero-oligomers, to alter their functions. G protein-coupled purinergic receptors, classified as adenosine receptors, and P2Y receptors (ATP receptors) are also found to oligomerize each other to alter their pharmacology. Specifically, adenosine receptor of A1 subtype (A1R) is able to form a heteromeric complex with P2Y receptor of P2Y1 type (P2Y1R) either in heterologously transfected cells or in rat brain tissues, as demonstrated by coimmunoprecipitation or bioluminescence resonance energy transfer methods in addition to double immunocytochemistry. It is shown that the heteromerization between A1R and P2Y1R generates an adenosine receptor with P2Y-like agonistic pharmacology, i.e., a potent P2Y1R agonist, adenosine 5′-O-(2-thiodiphosphate), binds the A1R binding pocket of the A1R/P2Y1R complex and inhibits adenylyl cyclase activity via Gi/o protein. This hetero-oligomerization between adenosine receptor and P2Y receptor might be one of the mechanisms for the adenine nucleotide-mediated inhibition of neurotransmitter release. The oligomerization of purinergic receptors is thus considered as an important regulation system in the central nervous system.

Index Entries

GPCR dimer oligomerization purinergic adenosine receptor P2 receptor BRET ATP inhibitory neurotransmission 

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Copyright information

© Humana Press Inc 2005

Authors and Affiliations

  • Hiroyasu Nakata
    • 1
  • Kazuaki Yoshioka
    • 1
  • Toshio Kamiya
    • 1
  • Hirofumi Tsuga
    • 1
  • Koshi Oyanagi
    • 1
  1. 1.Department of Molecular Cell SignalingTokyo Metropolitan Institute for NeuroscienceTokyoJapan

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