• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2007 Fiscal Year Final Research Report Summary

Molecular identification and functional analysis of a caffeine receptor on the plasma membrane.

Research Project

Project/Area Number 18390067
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General physiology
Research InstitutionNational Institute for Physiological Sciences

Principal Investigator

KUBO Yoshihiro  National Institute for Physiological Sciences, Department of Molecular Physiology, Professor (80211887)

Co-Investigator(Kenkyū-buntansha) SAITOH Osamu  Nagahama Institute of Bio-Science and Technology, Department of Bio-Science, Professor (60241262)
TATEYAMA Michihiro  National Institute for Physiological Sciences, Department of Molecular Physiology, Associate Professor (30276472)
Project Period (FY) 2006 – 2007
KeywordsPhysiology / Neuroscience / Biomolecule / Protein / Signal transduction
Research Abstract

Caffeine has various well-characterized pharmacological effects mediated e.g. via ryanodine receptor stimulation and phosphodiesterase inhibition. However, it was recently reported that application of caffeine to STC-1 mouse gastrointestinal endocrine cells induces a rapid increase in intracellular Ca^<2+> (Ca^<2+>; ) that is suppressed by inhibition of phospholipase C. This suggests a novel pharmacological action for caffeine. We observed that caffeine-induced increases in Ca^<2+>i in fura-2-loaded STC-1 cells were dependent on extracellular Ca^<2+> and were suppressed by TRP (Transient Receptor Potential) channel blockers. In addition, Ca^<2+>i imaging and electrophysiological analyses showed that mouse TRPA1 channels were activated by mM concentrations of caffeine in heterologous expression systems such as HEK293T cells and Xenopus oocytes. These responses to caffeine were confirmed in acutely dissociated dorsal root ganglion sensory neurons from wild-type (WT) mice, which are known to express TRPA1, but were not seen in neurons from TRPA1 knock-out (KO) mice. Expression of TRPA1 protein was detected immunohistochemically in nerve fibers and bundles in the mouse tongue. Moreover, WT mice, but not KO mice, showed a remarkable aversion to caffeine-containing water in two-bottle preference tests. Finally, we observed that the activity of human TRPA1 channels is suppressed by caffeine, in clear contrast to the mouse channels. Our findings demonstrated caffeine activates a Ca^<2+>-permeable TRPA1 channel in mouse but suppresses the activity of the human orthologue. We also showed that mouse TRPA1 channels expressed in sensory neurons cause an aversion to drinking caffeine-containing water, suggesting they mediate the perception of caffeine.

  • Research Products

    (14 results)

All 2008 2007 2006

All Journal Article (12 results) (of which Peer Reviewed: 6 results) Presentation (2 results)

  • [Journal Article] The motor protein prestin is a bullet-shaped molecule with inner Cavities2008

    • Author(s)
      Mio K, Kubo Y, Ogura T, Yamamoto T, Arisaka F and Sato C
    • Journal Title

      Journal of Biological Chemistry 283

      Pages: 1137-1145

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] The motor protein prestin is a bullet-shaped molecule with inner Cavities.2008

    • Author(s)
      Mio K, Kubo Y, Ogura T, Yamamoto T, Arisaka F, Sato C
    • Journal Title

      Journal of Biological Chemistry 283

      Pages: 1137-1145

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Coupling profile of the metabotropic glutamate receptor 1α is regulated by the C-terminal domain2007

    • Author(s)
      Tateyama M and Kubo Y
    • Journal Title

      Molecular and Cellular Neuroscience 34

      Pages: 445-452

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] KCNE1 and KCNE3 Stabilize and/or Slow Voltage Sensing S4 Segment of KCNQ1 Channel2007

    • Author(s)
      Nakajo K and Kubo Y
    • Journal Title

      Journal of General Physiology 130

      Pages: 269-281

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Coupling profile of the metabotropic glutamate receptor 1□is regulated by the C-terminal domain.2007

    • Author(s)
      Tateyama M, Kubo Y
    • Journal Title

      Molecular and Cellular Neuroscience 34

      Pages: 445-452

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] KCNE1 and KCNE3 Stabilize and/or Slow Voltage Sensing S4 Segment of KCNQ1 Channel.2007

    • Author(s)
      Nakajo K, Kubo Y
    • Journal Title

      Journal of General Physiology 130

      Pages: 269-281

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Alternative splicing of RGS8 gene changes the binding property to the M1 muscarinic receptor to confer receptor type-specific Gq regulation2006

    • Author(s)
      Itoh M, Nagatomo K, Kubo Y and Saitoh O
    • Journal Title

      Journal of Neurochemistry 99

      Pages: 1505-1516

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Regulation of the desensitization and ion selectivity of ATP-gated P2X_2 channels by phosphoinositides2006

    • Author(s)
      Fujiwara Y and Kubo Y
    • Journal Title

      Journal of Physiology 576

      Pages: 135-149

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Functional roles of charged amino acid residues on the wall of the cytoplasmic pore of Kir2.12006

    • Author(s)
      Fujiwara Y and Kubo Y
    • Journal Title

      Journal of General Physiology 127

      Pages: 401-419

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Alternative splicing of RGS8 gene changes the binding property to the Ml muscarinic receptor to confer receptor type-specific Gq regulation.2006

    • Author(s)
      Itoh M, Nagatomo K, Kubo Y, Saitoh O
    • Journal Title

      Journal of Neurochemistry 99

      Pages: 1505-1516

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Regulation of the desensitization and ion selectivity of ATP-gated P2X_2 channels by phosphoinositides.2006

    • Author(s)
      Fujiwara Y, Kubo Y
    • Journal Title

      Journal of Physiology 576

      Pages: 135-149

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Functional roles of charged amino acid residues on the wall of the cytoplasmic pore of Kir2.1.2006

    • Author(s)
      Fujiwara Y, Kubo Y
    • Journal Title

      Journal of General Physiology 127

      Pages: 401-419

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] TRPA1チャネルはカフェインにより活性化される2008

    • Author(s)
      長友 克広, 久保 義弘
    • Organizer
      第85回日本生理学会大会
    • Place of Presentation
      東京
    • Year and Date
      2008-03-25
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Activation of TRPA1 channel by caffeine2008

    • Author(s)
      Nagatomo K and Kubo Y
    • Organizer
      85th annual meeting of the Physiological Society of Japan
    • Place of Presentation
      Tokyo
    • Year and Date
      2008-03-25
    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 2010-02-04  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi