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


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.

SUBMITTER: Takayasu S 

PROVIDER: S-EPMC1464357 | biostudies-literature | 2006 May

REPOSITORIES: biostudies-literature

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

Takayasu Shinobu S   Sakurai Takeshi T   Iwasaki Satoshi S   Teranishi Hitoshi H   Yamanaka Akihiro A   Williams S Clay SC   Iguchi Haruhisa H   Kawasawa Yuka Imamura YI   Ikeda Yukio Y   Sakakibara Iori I   Ohno Kousaku K   Ioka Ryoichi X RX   Murakami Saori S   Dohmae Naoshi N   Xie Jian J   Suda Toshihiro T   Motoike Toshiyuki T   Ohuchi Takashi T   Yanagisawa Masashi M   Sakai Juro J  

Proceedings of the National Academy of Sciences of the United States of America 20060428 19


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 exclusive  ...[more]

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