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

doi:10.1021/ml1002053

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

64 Citations (Scopus)

Abstract

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 language	English
Pages (from-to)	53-57
Number of pages	5
Journal	ACS Medicinal Chemistry Letters
Volume	2
Issue number	1
DOIs	https://doi.org/10.1021/ml1002053
Publication status	Published - 2011 Jan 13
Externally published	Yes

Keywords

GPR54
NPFFR1
NPFFR2
Neuropeptide FF receptors
kisspeptin

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

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10.1021/ml1002053

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title = "Activation of neuropeptide FF receptors by kisspeptin receptor ligands",

abstract = "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.",

keywords = "GPR54, NPFFR1, NPFFR2, Neuropeptide FF receptors, kisspeptin",

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

year = "2011",

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doi = "10.1021/ml1002053",

language = "English",

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AU - Oishi, Shinya

AU - Misu, Ryosuke

AU - Tomita, Kenji

AU - Setsuda, Shohei

AU - Masuda, Ryo

AU - Ohno, Hiroaki

AU - Naniwa, Yousuke

AU - Ieda, Nahoko

AU - Inoue, Naoko

AU - Ohkura, Satoshi

AU - Uenoyama, Yoshihisa

AU - Tsukamura, Hiroko

AU - Maeda, Kei Ichiro

AU - Hirasawa, Akira

AU - Tsujimoto, Gozoh

AU - Fujii, Nobutaka

PY - 2011/1/13

Y1 - 2011/1/13

N2 - 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.

AB - 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.

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KW - NPFFR2

KW - Neuropeptide FF receptors

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Activation of neuropeptide FF receptors by kisspeptin receptor ligands

Abstract

Keywords

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