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Caffeine activates mouse TRPA1 channels but suppresses human TRPA1 channels

Katsuhiro Nagatomo1, Yoshihiro Kubo

  • 1Division of Biophysics and Neurobiology, National Institute for Physiological Sciences, Okazaki, Aichi 444-8585, Japan.

Proceedings of the National Academy of Sciences of the United States of America
|November 8, 2008
PubMed

Insights

Caffeine activates mouse TRPA1 channels in sensory neurons, leading to a taste aversion in mice. This suggests TRPA1 mediates the perception of caffeine, but it does not activate human TRPA1.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Sensory Physiology

Background:

  • Caffeine is widely consumed for its stimulant effects.
  • Mammalian plasma membrane receptors or ion channels activated by caffeine were previously unknown.
  • Transient Receptor Potential Ankyrin 1 (TRPA1) channels are involved in sensory perception.

Purpose of the Study:

  • To investigate the molecular targets of caffeine in mammals.
  • To determine if TRPA1 channels are activated by caffeine.
  • To elucidate the role of TRPA1 in caffeine perception and aversion.

Main Methods:

  • Heterologous expression systems for Ca(2+)(i) imaging and electrophysiological analyses.
  • Studies on acutely dissociated dorsal root ganglion sensory neurons from wild-type (WT) and TRPA1 knockout (KO) mice.
  • Immunohistochemical detection of TRPA1 expression in mouse tongue tissues.
  • Behavioral aversion tests using caffeine-containing water in WT and TRPA1 KO mice.

Main Results:

  • Caffeine activated mouse TRPA1 channels in heterologous systems and in sensory neurons.
  • TRPA1 KO mice did not exhibit the caffeine-induced aversion observed in WT mice.
  • TRPA1 was detected in nerve fibers and bundles in the mouse tongue.
  • Caffeine suppressed, rather than activated, human TRPA1 channels.

Conclusions:

  • Mouse TRPA1 channels expressed in sensory neurons mediate an aversion to drinking caffeine-containing water.
  • TRPA1 channels are suggested to be involved in the perception of caffeine in mice.
  • Caffeine's interaction with TRPA1 differs between mouse and human orthologs.

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