RFamide-related peptides signal through the neuropeptide FF receptor and regulate pain-related responses in the rat.
The mammalian RFamide-related peptide RFRP1 was found to signal through the neuropeptide FF 2 receptor expressed in Xenopus oocytes. The peptide induced a dose-dependent outward current, which was dependent on the simultaneous expression of GIRK1 and GIRK4 potassium channels. In neuropathic rats, RFRP1 administered intrathecally induced tactile antiallodynia and thermal antinociception, whereas in the solitary tract nucleus it produced only mechanical antihyperalgesia. Expression of the RFamide-related peptide mRNA in the rat CNS was distinctly different from that of neuropeptide FF. Most notably, the gene was not expressed in the hindbrain or spinal cord at detectable levels. However, there was a prominent group of RFamide-related peptide mRNA-expressing neurons in the central hypothalamus, in the area in and between the dorsomedial and ventromedial nuclei. The results suggest that RFamide-related peptides are potentially involved in pain regulation through a hypothalamo-medullary projection system, and possibly via action on neuropeptide FF 2 receptors. In neuropathic animals, the pain suppressive effect of RFamide-related peptide varies depending on the submodality of noxious test stimulation and the site of RFamide-related peptide administration.
Pertovaara
A
A
Department of Physiology, University of Turku, Turku, Finland. Antti.Pertovaara@helsinki.fi
Ostergård
M
M
Ankö
M-L
ML
Lehti-Koivunen
S
S
Brandt
A
A
Hong
W
W
Korpi
E R
ER
Panula
P
P
D000818:Animals; D003001:Cloning, Molecular / Q000379:methods; D004305:Dose-Response Relationship, Drug; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D008845:Microinjections / Q000379:methods; D009479:Neuropeptides / Q000008:administration & dosage* / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D018013:Receptors, Neuropeptide / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D017552:Solitary Nucleus / Q000187:drug effects / Q000503:physiopathology; D013116:Spinal Cord / Q000187:drug effects / Q000503:physiopathology; D014982:Xenopus laevis
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D009479:Neuropeptides; D024661:Potassium Channels, Inwardly Rectifying; C416987:RFamide peptide; D012333:RNA, Messenger; D018013:Receptors, Neuropeptide; C083929:neuropeptide FF receptor