Hetero‐oligomerization of adenosine A1 receptors with P2Y1 receptors in rat brains

FEBS Letters

Nakata, Hiroyasu¹  Yoshioka, Kazuaki¹  Hosoda, Ritsuko²  Kuroda, Yoichiro² 

[1] Department of Molecular Cell Signaling, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu, Tokyo 183-8526, Japan;Department of Molecular Neurobiology, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo 183-8526, Japan

关键词: Colocalization;    Purinergic;    Heteromer;    Immunohistochemistry;    A1R;    adenosine A1 receptor;    P2Y1R;    P2Y1 receptor;    GPCR;    G protein-coupled receptor;   

DOI  :  10.1016/S0014-5793(02)03540-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Adenosine and ATP modulate cellular and tissue functions via specific P1 and P2 receptors, respectively. Although, in general, adenosine inhibits excitability and ATP functions as an excitatory transmitter in the central nervous system, little is known about the direct interaction between P1 and P2 receptors. We recently demonstrated that the G_i/o-coupled adenosine A₁ receptor (A₁R) and G_q/11-coupled P2Y₁ receptor (P2Y₁R) form a heteromeric complex with a unique pharmacology in cotransfected HEK293T cells using the coimmunoprecipitation of differentially epitope-tagged forms of the receptor [Yoshioka et al. (2001) Proc. Natl. Acad. Sci. USA 98, 7617–7622], although it remained to be determined whether this hetero-oligomerization occurs in vivo. In the present study, we first demonstrated a high degree of colocalization of A₁R and P2Y₁R by double immunofluorescence experiments with confocal laser microscopy in rat cortex, hippocampus and cerebellum in addition to primary cultures of cortical neurons. Then, a direct association of A₁R with P2Y₁R was shown in coimmunoprecipitation studies using membrane extracts from these regions of rat brain. Together, these results suggest the widespread colocalization of A₁R and P2Y₁R in rat brain, and both receptors can exist in the same neuron, and therefore associate as hetero-oligomeric complexes in the rat brain.

【 授权许可】

Unknown