論文

査読有り
2007年6月

G protein-independent neuromodulatory action of adenosine on metabotropic glutamate signalling in mouse cerebellar Purkinje cells

JOURNAL OF PHYSIOLOGY-LONDON
  • Toshihide Tabata
  • ,
  • Daisuke Kawakami
  • ,
  • Kouichi Hashimoto
  • ,
  • Hidetoshi Kassai
  • ,
  • Takayuki Yoshida
  • ,
  • Yuki Hashimotodani
  • ,
  • Bertil B. Fredholm
  • ,
  • Yuko Sekino
  • ,
  • Atsu Aiba
  • ,
  • Masanobu Kano

581
2
開始ページ
693
終了ページ
708
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1113/jphysiol.2007.129866
出版者・発行元
WILEY-BLACKWELL PUBLISHING, INC

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 A(1)-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 Ca(2+) 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 Ca(2+) 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.

リンク情報
DOI
https://doi.org/10.1113/jphysiol.2007.129866
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/17379632
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000246756000025&DestApp=WOS_CPL
ID情報
  • DOI : 10.1113/jphysiol.2007.129866
  • ISSN : 0022-3751
  • PubMed ID : 17379632
  • Web of Science ID : WOS:000246756000025

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