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Suppressive effect of transient receptor potential vanilloid 1 on olfactory receptor signal transduction

Sakura Moriyama1,2, Shuji Hinuma1, Shun'ichi Kuroda1,2

  • 1SANKEN, The University of Osaka, Mihogaoka 8-1, Ibaraki, Osaka, Japan.

Bioscience, Biotechnology, and Biochemistry
|June 28, 2025
PubMed

Insights

Transient Receptor Potential Vanilloid 1 (TRPV1) activation suppresses olfactory receptor (OR) signaling by increasing intracellular calcium. This calcium influx activates G protein-coupled receptor kinase (GRK), modulating OR responses.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Sensory Science

Background:

  • Olfactory receptors (ORs) detect odorants through signaling pathways involving cyclic adenosine monophosphate (cAMP).
  • Transient Receptor Potential Vanilloid 1 (TRPV1) is a calcium-permeable ion channel implicated in sensory perception.

Purpose of the Study:

  • To investigate the influence of TRPV1 on ligand-stimulated OR activation.
  • To elucidate the molecular mechanisms underlying TRPV1-mediated modulation of OR signaling.

Main Methods:

  • Co-expression of TRPV1 and OR51E1 in HEK293T cells.
  • Stimulation with isovaleric acid and capsaicin.
  • Measurement of intracellular cAMP levels.
  • RNA interference (siRNA) targeting TRPV1.
  • Extracellular calcium depletion experiments.
  • Use of calcium ionophore (A23187) and GRK inhibitor (CCG21022).

Main Results:

  • TRPV1 co-expression suppressed OR51E1 activation by isovaleric acid, an effect potentiated by capsaicin.
  • Capsaicin alone suppressed OR51E1-mediated cAMP production.
  • Endogenous TRPV1, targeted by siRNA, was involved in capsaicin's suppressive effect.
  • TRPV1-dependent suppression was abolished by extracellular calcium depletion.
  • Calcium ionophore mimicked TRPV1 effects, and its action was blocked by a GRK inhibitor.

Conclusions:

  • TRPV1 activation suppresses OR signaling through calcium (Ca²⁺) influx.
  • This calcium influx subsequently activates G protein-coupled receptor kinase (GRK).
  • TRPV1 acts as a negative regulator of olfactory receptor responses via a calcium-GRK pathway.
Keywords:
Ca2+ influxG protein-coupled receptor kinaseolfactory receptorsphosphorylationtransient receptor potential vanilloid 1

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