title: Neuropeptide FF and FMRFamide potentiate acid-evoked currents from sensory neurons and proton-gated DEG/ENaC channels.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City 52242, USA.
authors.forename: C C
authors.initials: CC
authors.lastname: Askwith
authors.forename: C
authors.initials: C
authors.lastname: Cheng
authors.forename: M
authors.initials: M
authors.lastname: Ikuma
authors.forename: C
authors.initials: C
authors.lastname: Benson
authors.forename: M P
authors.initials: MP
authors.lastname: Price
authors.forename: M J
authors.initials: MJ
authors.lastname: Welsh
mesh_terms: D062565:Acid Sensing Ion Channels; D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D062626:Degenerin Sodium Channels; D053503:Epithelial Sodium Channels; D019835:FMRFamide / Q000494:pharmacology* / Q000502:physiology; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007473:Ion Channels / Q000187:drug effects* / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000187:drug effects* / Q000502:physiology; D009479:Neuropeptides / Q000494:pharmacology* / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology* / Q000502:physiology; D051381:Rats; D014981:Xenopus
chemical_list: C568424:ASIC2 protein, human; D062565:Acid Sensing Ion Channels; C568425:Asic2 protein, rat; D062626:Degenerin Sodium Channels; D053503:Epithelial Sodium Channels; D007473:Ion Channels; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D009842:Oligopeptides; D019835:FMRFamide; C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide