1999 Fiscal Year Final Research Report Summary
Search for novel neuropeptides using orphan receptor expressing cell systems.
| Project/Area Number |
10680736
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
KOJIMA Masayasu National Cardiovascular Center Research Institute, Head of Biochemistry, 生化学部, 室長 (20202062)
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| Co-Investigator(Kenkyū-buntansha) |
KANGAWA Kenji National Cardiovascular Center Research Institute, Director of Biochemistry, 生化学部, 部長 (00112417)
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| Project Period (FY) |
1998 – 1999
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| Keywords | Growth hormone / Growth hormone secretagogue / Stomach / Orphan receptor / Gherelin / n-Octanoylation / Hypothalamus / Pituitary |
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| Research Abstract |
Small synthetic molecules termed growth hormone secretagogues (GHSs) act through an orphan G-protein coupled receptor, GHS-R, to stimulate growth hormone (GH) release from pituitary. Recent cloning of GHS-R strongly suggests the presence of an endogenous ligand for the receptor, and of a mechanism for GH-regulation distinct from that by hypothalamic growth hormone-releasing hormone (GHRH). We report here purification and identification in rat stomach of a new endogenous ligand specific for GHS-R. The purified ligand is a novel peptide consisting of 28 amino acids, in which the Ser-3 residue is n-octanoylated. The acylas peptide specifically releases GH in vivo as well as in vitro. O-n-octanoylation at Ser-3 is essential to the activity. We designate the GH-releasing peptide "GHRELIN" ("ghre" is the Proto-Indo-European root of the word "grow"). Human ghrelin is highly homologous to rat ghrelin except that only two amino acids are replaced. Occurrence of ghrelin in both rat and human indicates that GH release from pituitary may be regulated not only by hypothalamic GHRH, but also by ghrelin newly identified.
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