| Co-Investigator(Kenkyū-buntansha) |
KOJIMA Masayasu Kurume University, Institute of lifescience Molecuar Genetics, Professor, 分子生命科学研究所遺伝子情報研究部門, 教授 (20202062)
MIYAZATO Mikiya National Cardiovascular Center Research Institute, Head of Biochemistry, 生化学部, 室長 (50291183)
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| Research Abstract |
In this research project, we have analyzed the physiological functions of the novel ligands recently discovered by our group, and also searched for endogenous ligands of orphan GPCRs. We obteined fruitful results from this study as listed below.
1. Elucidation of physiological functions of ghrelin, a growth hormone (GH)- releasing and orexigenic peptide :
Ghrelin was discovered in the stomach as a GH-releasing peptide, and is known that it is mainly produced and secreted in the stomach, and has potent stimulating activities on GH release and appetite. In the present study, it is shown that ghrelin is also produced in the hypothalamus and peripheral tissues other than stomach, and has various central and peripheral regulatory roles in digestive tract, energy metabolism, cardiovascular system and regeneration of tissues. The research of ghrelin is now proceeding for clinical application. On the other hand, desacyl-ghrelin, lacking fatty acid modification of ghrelin and known to be an inactive form, is shown to have physiological function in cellular proliferation via unidentified receptor other than GHS-R.
2. Elucidation of physiological functions of Neuromedin U (NMU), an anorectic peptide :
In this study, novel functions of NMU are clarified such as anorectic activity, and the roles in stress response and metabolism. It should be noted that we have identified NMU as a novel regulatory factor of circadian rhythm.
3. Search for novel endogenous ligands by using assay systems of orphan receptor expressing cells :
In this study, we have succeeded in discovering a novel peptide, Neuromedin S (NMS), from rat brain. We also revealed very interesting facts that NMS, restrictedly expressed in suprachiasmatic nuclei (SCN) in the brain, has a role in regulating circadian rhythm by the mechanism different from NMU, and has more potent anorectic activity than NMU.
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