Analysis of feeding and lipid metabolism regulation by bombesin-like peptide receptors.
| Project/Area Number |
15500207
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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 |
Neuroscience in general
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
OHKI Hiroko Tokyo Medical and Dental University, Medical Research Institute, Associate Professor, 難治疾患研究所, 助教授 (00211483)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | bombesin-like peptide receptors / BRS-3 / GRP-R / leptin / melanin-concentrating hormone / obesity / hyperphagia / BRS-3.5 |
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| Research Abstract |
To clarify the mechanism underlying modulation of feeding and metabolism by BRS-3, we investigated the relationship between BRS-3 and other feeding-regulating peptides and their receptors. In BRS-3-deficient mice, we found hyperphagia, subsequent hyperleptinemia and brain leptin resistance. Among orexigenic neuropeptides, the hyperphagic response to melanin-concentrating hormone (MCH) was significantly enhanced in BRS-3-deficient mice. In addition, the levels of MCH-R and MCH mRNAs in the hypothalamus were significantly elevated. From these results, we assume that the BRS-3 regulate the mechanism by which leptin decreases the MCH/MCH-R signaling. To generate mouse line conditionally expressing BRS-3, we constructed the vector and introduced it into ES cells and obtained the chimeric mice. We also have successfully cloned two bombesin-like peptide receptors, chGRP-R and chBRS-3.5 from chick brain. ChGRP-R is highly identical with mammalian and amphibian GRP-R, and this receptor showed high affinity for both GRP and bombesin. ChBRS-3.5, having sequence similarities to both mammalian BRS-3 and amphibian BB4, showed moderate affinity for bombesin, but low affinity for both GRP and NMB. In chick brain, chGRP-R is expressed predominantly in the hypothalamus whereas chBRS-3.5 is distributed widely in the pallium. These results recapitulate important roles of bombesin peptide receptors in vertebrates.
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Report
(3 results)
Research Products
(15 results)
