NPY mediates ATP-induced neuroproliferation in adult mouse olfactory epithelium

Neurobiol Dis. 2010 Jun;38(3):405-13. doi: 10.1016/j.nbd.2010.02.013. Epub 2010 Mar 6.


In the CNS, ATP is released upon injury and promotes neuroproliferation via purinergic receptors. In the olfactory epithelium, ATP promotes the synthesis and release of neurotrophic factor NPY in neonates and induces neuroproliferation in neonatal and adult mice. We tested the hypothesis that NPY is involved in ATP-induced neuroproliferation in adult mice olfactory epithelium. Intranasal instillation of ATP significantly increased protein levels and number of NPY(+) cells. Pre-intranasal instillation of purinergic receptor antagonist PPADS significantly reduced ATP-induced upregulation of NPY. Intranasal instillation of NPY-Y1 receptor antagonist BIBP3226 following ATP instillation significantly inhibited the ATP-induced increase in BrdU incorporation, suggesting that NPY is released after ATP instillation and activates Y1 receptors to promote neuroproliferation. These data indicate that ATP initiates neuroproliferation via NPY upregulation, NPY release, and Y1 receptor activation, and suggests that the olfactory epithelium is good model to study neuroregenerative mechanisms in the CNS.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Aging
  • Animals
  • Arginine / administration & dosage
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Male
  • Mice
  • Models, Neurological
  • Neurogenesis / drug effects
  • Neurogenesis / physiology*
  • Neuropeptide Y / metabolism*
  • Olfactory Mucosa / drug effects
  • Olfactory Mucosa / physiology*
  • Purinergic Antagonists
  • Pyridoxal Phosphate / analogs & derivatives
  • Pyridoxal Phosphate / pharmacology
  • Receptors, Neuropeptide Y / antagonists & inhibitors
  • Receptors, Neuropeptide Y / metabolism*
  • Receptors, Purinergic / metabolism
  • Sensory Receptor Cells / drug effects
  • Sensory Receptor Cells / physiology


  • BIBP 3226
  • Neuropeptide Y
  • Npy1r protein, mouse
  • Purinergic Antagonists
  • Receptors, Neuropeptide Y
  • Receptors, Purinergic
  • pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid
  • Pyridoxal Phosphate
  • Adenosine Triphosphate
  • Arginine