Human kisspeptins activate neuropeptide FF2 receptor

Neuroscience. 2010 Sep 29;170(1):117-22. doi: 10.1016/j.neuroscience.2010.06.058. Epub 2010 Jul 1.


We studied the possible activation of a neuropeptide FF2 receptor (NPFF2R) by kisspeptins, neuropeptides derived from the mouse and human metastin or Kiss-1 precursor. The hypothesis was that the human kisspeptins, which share the C-terminal dipeptide RF-NH(2) with NPFF, might activate the NPFF2R, as has previously been shown for two related peptides, prolactin-releasing peptide and RF-amide-related peptide. Using two-electrode voltage clamp of Xenopus oocytes, we found that 100 nM NPFF strongly activated the human NPFF2R expressed together with rat GIRK1/4 inward rectifier potassium channels, and that 100 nM hKisspeptin-13 and hKisspeptin-8 had about 25% relative efficacy to that of NPFF. The current response induced by hKisspeptin-13 was proportional to its concentration (1-500 nM). The corresponding mouse peptides resulted in low activation only. When hNPFF2R was expressed in Chinese hamster ovary (CHO) cells, NPFF and its stable analog (1DMe)Y8Fa induced guanosine 5'-(gamma-[(35)S]thio)-triphosphate (GTP-gamma-[(35)S]) binding with EC(50) values of 13+/-4 and 16+/-4 nM, respectively. hKisspeptin-13 induced the binding with an EC(50) value of 110+/-50 nM, whereas mKisspeptin-13 induced very modestly activation with an EC(50) value>2 microM. The results suggest that, besides regulation of reproduction, kisspeptins have a potential to mediate physiological effects on, for example autonomic regulation and nociception in man via the NPFF2R pathways.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Female
  • Humans
  • Kisspeptins
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neural Pathways / physiology
  • Protein Binding / physiology
  • Rats
  • Receptors, Neuropeptide / agonists*
  • Receptors, Neuropeptide / metabolism*
  • Reproduction / physiology
  • Tumor Suppressor Proteins / physiology*
  • Xenopus laevis


  • KISS1 protein, human
  • Kisspeptins
  • Receptors, Neuropeptide
  • Tumor Suppressor Proteins
  • neuropeptide FF receptor