A neuropeptide ligand of the G protein-coupled receptor GPR103 regulates feeding, behavioral arousal, and blood pressure in mice

Shinobu Takayasu, Takeshi Sakurai, Satoshi Iwasaki, Hitoshi Teranishi, Akihiro Yamanaka, S. Clay Williams, Haruhisa Iguchi, Yuka Imamura Kawasawa, Yukio Ikeda, Iori Sakakibara, Kousaku Ohno, Ryoichi X. Ioka, Saori Murakami, Naoshi Dohmae, Jian Xie, Toshihiro Suda, Toshiyuki Motoike, Takashi Ohuchi, Masashi Yanagisawa, Juro Sakai

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

Here, we report the isolation and characterization of an endogenous peptide ligand of GPR103 from rat brains. The purified peptide was found to be the 43-residue RF-amide peptide QRFP. We also describe two mouse homologues of human GPR103, termed mouse GPR103A and GPR103B. QRFP binds and activates the human GPR103, as well as mouse GPR103A and GPR103B, with nanomolar affinities in transfected cells. Systematic in situ hybridization analysis in mouse brains showed that QRFP is expressed exclusively in the periventricular and lateral hypothalamus, whereas the two receptor mRNAs are distinctly localized in various brain areas without an overlap to each other. When administered centrally in mice, QRFP induced feeding behavior, accompanied by increased general locomotor activity and metabolic rate. QRFP-induced food intake was abolished by preadministration of BIBP3226, a specific antagonist for the Y1 neuropeptide Y receptor. Hypothalamic prepro-QRFP mRNA expression was up-regulated upon fasting and in genetically obese ob/ob and db/db mice. Central QRFP administration also evoked highly sustained elevation of blood pressure and heart rate, Our findings suggest that QRFP and GPR103A/B may regulate diverse neuroendocrine and behavioral functions and implicate this neuropeptide system in metabolic syndrome.

Original languageEnglish (US)
Pages (from-to)7438-7443
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number19
DOIs
StatePublished - May 9 2006

Fingerprint

G-Protein-Coupled Receptors
Arousal
Neuropeptides
Blood Pressure
Ligands
Brain
Lateral Hypothalamic Area
Messenger RNA
Peptides
Feeding Behavior
Locomotion
Amides
In Situ Hybridization
Fasting
Eating
Heart Rate

Keywords

  • Grooming
  • Hypothalamus
  • Metabolic syndrome
  • QRFP
  • Wakefulness

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

A neuropeptide ligand of the G protein-coupled receptor GPR103 regulates feeding, behavioral arousal, and blood pressure in mice. / Takayasu, Shinobu; Sakurai, Takeshi; Iwasaki, Satoshi; Teranishi, Hitoshi; Yamanaka, Akihiro; Williams, S. Clay; Iguchi, Haruhisa; Kawasawa, Yuka Imamura; Ikeda, Yukio; Sakakibara, Iori; Ohno, Kousaku; Ioka, Ryoichi X.; Murakami, Saori; Dohmae, Naoshi; Xie, Jian; Suda, Toshihiro; Motoike, Toshiyuki; Ohuchi, Takashi; Yanagisawa, Masashi; Sakai, Juro.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 19, 09.05.2006, p. 7438-7443.

Research output: Contribution to journalArticle

Takayasu, S, Sakurai, T, Iwasaki, S, Teranishi, H, Yamanaka, A, Williams, SC, Iguchi, H, Kawasawa, YI, Ikeda, Y, Sakakibara, I, Ohno, K, Ioka, RX, Murakami, S, Dohmae, N, Xie, J, Suda, T, Motoike, T, Ohuchi, T, Yanagisawa, M & Sakai, J 2006, 'A neuropeptide ligand of the G protein-coupled receptor GPR103 regulates feeding, behavioral arousal, and blood pressure in mice', Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 19, pp. 7438-7443. https://doi.org/10.1073/pnas.0602371103
Takayasu, Shinobu ; Sakurai, Takeshi ; Iwasaki, Satoshi ; Teranishi, Hitoshi ; Yamanaka, Akihiro ; Williams, S. Clay ; Iguchi, Haruhisa ; Kawasawa, Yuka Imamura ; Ikeda, Yukio ; Sakakibara, Iori ; Ohno, Kousaku ; Ioka, Ryoichi X. ; Murakami, Saori ; Dohmae, Naoshi ; Xie, Jian ; Suda, Toshihiro ; Motoike, Toshiyuki ; Ohuchi, Takashi ; Yanagisawa, Masashi ; Sakai, Juro. / A neuropeptide ligand of the G protein-coupled receptor GPR103 regulates feeding, behavioral arousal, and blood pressure in mice. In: Proceedings of the National Academy of Sciences of the United States of America. 2006 ; Vol. 103, No. 19. pp. 7438-7443.
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AU - Takayasu, Shinobu

AU - Sakurai, Takeshi

AU - Iwasaki, Satoshi

AU - Teranishi, Hitoshi

AU - Yamanaka, Akihiro

AU - Williams, S. Clay

AU - Iguchi, Haruhisa

AU - Kawasawa, Yuka Imamura

AU - Ikeda, Yukio

AU - Sakakibara, Iori

AU - Ohno, Kousaku

AU - Ioka, Ryoichi X.

AU - Murakami, Saori

AU - Dohmae, Naoshi

AU - Xie, Jian

AU - Suda, Toshihiro

AU - Motoike, Toshiyuki

AU - Ohuchi, Takashi

AU - Yanagisawa, Masashi

AU - Sakai, Juro

PY - 2006/5/9

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N2 - Here, we report the isolation and characterization of an endogenous peptide ligand of GPR103 from rat brains. The purified peptide was found to be the 43-residue RF-amide peptide QRFP. We also describe two mouse homologues of human GPR103, termed mouse GPR103A and GPR103B. QRFP binds and activates the human GPR103, as well as mouse GPR103A and GPR103B, with nanomolar affinities in transfected cells. Systematic in situ hybridization analysis in mouse brains showed that QRFP is expressed exclusively in the periventricular and lateral hypothalamus, whereas the two receptor mRNAs are distinctly localized in various brain areas without an overlap to each other. When administered centrally in mice, QRFP induced feeding behavior, accompanied by increased general locomotor activity and metabolic rate. QRFP-induced food intake was abolished by preadministration of BIBP3226, a specific antagonist for the Y1 neuropeptide Y receptor. Hypothalamic prepro-QRFP mRNA expression was up-regulated upon fasting and in genetically obese ob/ob and db/db mice. Central QRFP administration also evoked highly sustained elevation of blood pressure and heart rate, Our findings suggest that QRFP and GPR103A/B may regulate diverse neuroendocrine and behavioral functions and implicate this neuropeptide system in metabolic syndrome.

AB - Here, we report the isolation and characterization of an endogenous peptide ligand of GPR103 from rat brains. The purified peptide was found to be the 43-residue RF-amide peptide QRFP. We also describe two mouse homologues of human GPR103, termed mouse GPR103A and GPR103B. QRFP binds and activates the human GPR103, as well as mouse GPR103A and GPR103B, with nanomolar affinities in transfected cells. Systematic in situ hybridization analysis in mouse brains showed that QRFP is expressed exclusively in the periventricular and lateral hypothalamus, whereas the two receptor mRNAs are distinctly localized in various brain areas without an overlap to each other. When administered centrally in mice, QRFP induced feeding behavior, accompanied by increased general locomotor activity and metabolic rate. QRFP-induced food intake was abolished by preadministration of BIBP3226, a specific antagonist for the Y1 neuropeptide Y receptor. Hypothalamic prepro-QRFP mRNA expression was up-regulated upon fasting and in genetically obese ob/ob and db/db mice. Central QRFP administration also evoked highly sustained elevation of blood pressure and heart rate, Our findings suggest that QRFP and GPR103A/B may regulate diverse neuroendocrine and behavioral functions and implicate this neuropeptide system in metabolic syndrome.

KW - Grooming

KW - Hypothalamus

KW - Metabolic syndrome

KW - QRFP

KW - Wakefulness

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