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This Article Full Text Full Text (PDF) Supplemental data All Versions of this Article: 581/2/693    most recent jphysiol.2007.129866v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tabata, T. Articles by Kano, M. Search for Related Content PubMed PubMed Citation Articles by Tabata, T. Articles by Kano, M. Related Collections Neuroscience

¹ Department of Cellular Neuroscience, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan
² Division of Cell Biology, Department of Molecular and Cellular Biology, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan
³ Division of Neurophysiology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan
⁴ Department of Physiology and Pharmacology, Karolinska Institutet, S-171 77 Stockholm, Sweden
⁵ Department of Neurobiology and Behaviour, Gunma University Graduate School of, Medicine, Maebashi, Gunma 371-8511, Japan

Adenosine receptors (ARs) are G protein-coupled receptors (GPCRs) mediating the neuromodulatory actions of adenosine that influence emotional, cognitive, motor, and other functions in the central nervous system (CNS). Previous studies show complex formation between ARs and metabotropic glutamate receptors (mGluRs) in heterologous systems and close colocalization of ARs and mGluRs in several central neurons. Here we explored the possibility of intimate functional interplay between G_i/o protein-coupled A₁-subtype AR (A1R) and type-1 mGluR (mGluR1) naturally occurring in cerebellar Purkinje cells. Using a perforated-patch voltage-clamp technique, we found that both synthetic and endogenous agonists for A1R induced continuous depression of a mGluR1-coupled inward current. A1R agonists also depressed mGluR1-coupled intracellular Ca²⁺ mobilization monitored by fluorometry. A1R indeed mediated this depression because genetic depletion of A1R abolished it. Surprisingly, A1R agonist-induced depression persisted after blockade of G_i/o protein. The depression appeared to involve neither the cAMP-protein kinase A cascade downstream of the alpha subunits of G_i/o and G_s proteins, nor cytoplasmic Ca²⁺ that is suggested to be regulated by the beta-gamma subunit complex of G_i/o protein. Moreover, A1R did not appear to affect G_q protein which mediates the mGluR1-coupled responses. These findings suggest that A1R modulates mGluR1 signalling without the aid of the major G proteins. In this respect, the A1R-mediated depression of mGluR1 signalling shown here is clearly distinguished from the A1R-mediated neuronal responses described so far. These findings demonstrate a novel neuromodulatory action of adenosine in central neurons.

(Received 5 February 2007; accepted after revision 16 March 2007; first published online 22 March 2007)
Corresponding author M. Kano: Department of Cellular Neuroscience, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan. Email: mkano{at}cns.med.osaka-u.ac.jp

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