TRPV3 regulates nitric oxide synthase-independent nitric oxide synthesis in the skin

Nat Commun. 2011 Jun 28;2:369. doi: 10.1038/ncomms1371.


Nitric oxide (NO) is an unstable signalling molecule synthesized de novo mainly from L-arginine by NO synthase (NOS) enzymes. Nitrite reduction can also produce NO, predominantly within body fluids (for example, saliva, sweat and blood plasma) and under extreme hypoxic and acidic conditions. It remains unknown if intracellular canonical signalling pathways regulate nitrite-dependent NO production. Here we examine NO production in the skin, a hypoxic tissue enriched in nitrites wherein NO has important roles in wound healing and other biological processes. We show that activation of TRPV3, a heat-activated transient receptor potential ion channel expressed in keratinocytes, induces NO production via a nitrite-dependent pathway. TRPV3 and nitrite are involved in keratinocyte migration in vitro and in wound healing and thermosensory behaviours in vivo. Our study demonstrates that activation of an ion channel can induce NOS-independent NO production in keratinocytes.

MeSH terms

  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Cell Proliferation
  • Cells, Cultured
  • DNA Primers / genetics
  • Electroporation
  • Keratinocytes / metabolism*
  • Keratinocytes / physiology
  • Mice
  • Nitric Oxide / biosynthesis*
  • Nitrites / metabolism
  • Polymerase Chain Reaction
  • TRPV Cation Channels / metabolism*
  • Wound Healing / physiology


  • DNA Primers
  • Nitrites
  • TRPV Cation Channels
  • Trpv3 protein, mouse
  • Nitric Oxide