Activation of neuropeptide FF receptors by kisspeptin receptor ligands

Shinya Oishi, Ryosuke Misu, Kenji Tomita, Shohei Setsuda, Ryo Masuda, Hiroaki Ohno, Yousuke Naniwa, Nahoko Ieda, Naoko Inoue, Satoshi Ohkura, Yoshihisa Uenoyama, Hiroko Tsukamura, Kei Ichiro Maeda, Akira Hirasawa, Gozoh Tsujimoto, Nobutaka Fujii

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51 Citations (Scopus)


Kisspeptin is a member of the RFamide neuropeptide family that is implicated in gonadotropin secretion. Because kisspeptin-GPR54 signaling is implicated in the neuroendocrine regulation of reproduction, GPR54 ligands represent promising therapeutic agents against endocrine secretion disorders. In the present study, the selectivity profiles of GPR54 agonist peptides were investigated for several GPCRs, including RFamide receptors. Kisspeptin-10 exhibited potent binding and activation of neuropeptide FF receptors (NPFFR1 and NPFFR2). In contrast, short peptide agonists bound with much lower affinity to NPFFRs while showing relatively high selectivity toward GPR54. The possible localization of secondary kisspeptin targets was also demonstrated by variation in the levels of GnRH release from the median eminence and the type of GPR54 agonists used. Negligible affinity of the reported NPFFR ligands to GPR54 was observed and indicates the unidirectional cross-reactivity between both ligands.

Original languageEnglish
Pages (from-to)53-57
Number of pages5
JournalACS Medicinal Chemistry Letters
Issue number1
Publication statusPublished - 2011 Jan 13
Externally publishedYes



  • GPR54
  • kisspeptin
  • Neuropeptide FF receptors
  • NPFFR1
  • NPFFR2

ASJC Scopus subject areas

  • Organic Chemistry
  • Drug Discovery
  • Biochemistry

Cite this

Oishi, S., Misu, R., Tomita, K., Setsuda, S., Masuda, R., Ohno, H., Naniwa, Y., Ieda, N., Inoue, N., Ohkura, S., Uenoyama, Y., Tsukamura, H., Maeda, K. I., Hirasawa, A., Tsujimoto, G., & Fujii, N. (2011). Activation of neuropeptide FF receptors by kisspeptin receptor ligands. ACS Medicinal Chemistry Letters, 2(1), 53-57.