2002 Fiscal Year Final Research Report Summary
Search and functional analysis for novel bioactive peptides associated with regulation of energy balance and feeding behavior
| Project/Area Number |
13671170
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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 |
Endocrinology
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| Research Institution | National Cardiovasculer Center Reseach Institute |
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Principal Investigator |
MIYAZATO Mikiya Head of Biochemistry, 生化学部, 室長 (50291183)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAZATO Masamitsu Miyazaki Medical College Full Time Lecture, 医学部, 講師 (10180267)
KANGAWA Kenji Director of Biochemistry, 生化学部, 部長 (00112417)
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| Project Period (FY) |
2001 – 2002
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| Keywords | feeding / energy balance / orphan receptor / BRS-3 / peptide |
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| Research Abstract |
Obesity is one of the most serious problems worldwide, because it is associated with lifestyle-related disease such as hypertension, cardiovascular disease and type 2 diabetes. The aims of this study are to identify endogenous ligands for orphan GPCRs associated with regulation of energy balance and feeding behavior, and to clarify the biochemical and pathophysiological significance of the ligands.
We established stable mammalian cell lines expressing human BRS-3 or other orphan GPCRs to monitor changes in the intracellular second messenger that were induced by rat tissue extracts. Changes in the intracellular calcium concentration and cyclic AMP were measured using the FLIPR System (Molecular Device) and AlphaScreen (Packard), respectively. Several [Ca^<2+>]I-increasing activities for BRS-3 were found in rat brain and intestinal extracts. These were further purified by successive chromatography to prove known peptides, having cross-reactivity to BRS-3. The highest [Ca^<2+>]I-increasing activity for one other orphan receptor was found in rat brain extract. This was finally purified as a single peptide, and partial amino acid sequence indicated that this was a novel peptide. This peptide inhibited food intake in rats when injected intracerebroventricularly.
Ghrelin, a novel peptide purified from stomach as an endogenous ligand for the growth hormone secretagogue receptor in our laboratory, is an acylated peptide that stimulates food intake and the secretion of growth hormone. A single intravenous injection of somatostatin reduced the systemic plasma concentration of ghrelin in rats, and continuous infusion of somatostatin into the gastric artery of the vascularly perfused rat stomach suppressed ghrelin secretion. These findings indicate that ghrelin secretion from the stomach is regulated by gastric somatostatin.
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[Publications] Mitsushi Shimada, Yukari Date, Muhtashan S. Mondal, Koji Toshinai, Takuya Shimbara, Kyoko Fukunaga, Noboru Murakami, Mikiya Miyazato, Kenji Kangawa, Hironobu Yoshimatsu, Hisayuki Matsuo and Masamitsu Nakazato: "Somatostain suppresses ghrelin secretion from the rat stomach"Biochemical and Biophysical Research Communications. 302. 520-525 (2003)
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