Abstract:
: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.
journal_name
FEBS Lettjournal_title
FEBS lettersauthors
Yoshioka K,Hosoda R,Kuroda Y,Nakata Hdoi
10.1016/s0014-5793(02)03540-8keywords:
subject
Has Abstractpub_date
2002-11-06 00:00:00pages
299-303issue
2eissn
0014-5793issn
1873-3468pii
S0014579302035408journal_volume
531pub_type
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