Neuropeptide FF and FMRFamide potentiate acid-evoked currents from sensory neurons and proton-gated DEG/ENaC channels

Neuron. 2000 Apr;26(1):133-41. doi: 10.1016/s0896-6273(00)81144-7.


Acidosis is associated with inflammation and ischemia and activates cation channels in sensory neurons. Inflammation also induces expression of FMRFamidelike neuropeptides, which modulate pain. We found that neuropeptide FF (Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe amide) and FMRFamide (Phe-Met-Arg-Phe amide) generated no current on their own but potentiated H+-gated currents from cultured sensory neurons and heterologously expressed ASIC and DRASIC channels. The neuropeptides slowed inactivation and induced sustained currents during acidification. The effects were specific; different channels showed distinct responses to the various peptides. These results suggest that acid-sensing ion channels may integrate multiple extracellular signals to modify sensory perception.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Sensing Ion Channels
  • Action Potentials / drug effects*
  • Action Potentials / physiology
  • Animals
  • Cells, Cultured
  • Degenerin Sodium Channels
  • Epithelial Sodium Channels
  • FMRFamide / pharmacology*
  • FMRFamide / physiology
  • Ganglia, Spinal / drug effects*
  • Ganglia, Spinal / physiology
  • Humans
  • Ion Channels / drug effects*
  • Ion Channels / physiology
  • Nerve Tissue Proteins / drug effects*
  • Nerve Tissue Proteins / physiology
  • Neuropeptides / pharmacology*
  • Neuropeptides / physiology
  • Oligopeptides / pharmacology*
  • Oligopeptides / physiology
  • Rats
  • Xenopus


  • ASIC2 protein, human
  • Acid Sensing Ion Channels
  • Asic2 protein, rat
  • Degenerin Sodium Channels
  • Epithelial Sodium Channels
  • Ion Channels
  • Nerve Tissue Proteins
  • Neuropeptides
  • Oligopeptides
  • FMRFamide
  • phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide