Identification and characterization of a potential drug target regulating the pace of the central circadian clock in the brain
| Project/Area Number |
26293013
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Kyoto University |
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Principal Investigator |
Doi Masao 京都大学, 薬学研究科(研究院), 准教授 (20432578)
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| Co-Investigator(Renkei-kenkyūsha) |
OKAMURA Hitoshi 京都大学, 大学院薬学研究科, 教授 (60158813)
Jean-Michel Fustin 京都大学, 大学院薬学研究科, 特定講師 (50711818)
KOBAYASHI Takuya 京都大学, 医学部, 准教授 (20311730)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2016: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2015: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2014: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
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| Keywords | G蛋白質共役型受容体 / 体内時計 / オーファン受容体 / 視交叉上核 / G蛋白質共役受容体 / 概日時計 / GPCR |
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| Outline of Final Research Achievements |
The suprachiasmatic nucleus (SCN), the brain’s circadian pacemaker, governs daily rhythms in behavior and physiology. Here we identified and characterized Gpr176 as an SCN-enriched orphan G-protein coupled receptor (GPCR) that sets the pace of the central clock（Doi et al, Nat Commun 2016）. Interestingly, even in the absence of known ligand, Gpr176 has an agonist-independent basal activity to reduce cAMP signaling. A unique cAMP-repressing G-protein subclass Gz is required for the activity of Gpr176. The discovery of the functional orphan GPCR with a novel mode of action within the SCN would be of help to understand the mechanism that underpins the SCN and thereby facilitate searching for a potential specific drug target to modulate the central clock.
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Report
(4 results)
Research Products
(76 results)
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[Journal Article] Gpr176 is a Gz-linked orphan G-protein coupled receptor that sets the pace of circadian behavior.2016
Author(s)
Doi M, Murai I, Kunisue S, Setsu G, Uchio N, Tanaka R, Kobayashi S, Shimatani H, Hayashi H, Chao HW, Nakagawa Y, Takahashi Y, Hotta Y, Yasunaga JI, Matsuoka M, Hastings MH, Kiyonari H, and Okamura H.
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Journal Title
Nat Commun
Volume: 7
Issue: 1
Pages: 10583-10583
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] 3ß-hydroxysteroid dehydrogenase isoforms in human aldosterone-producing adenoma2015
Author(s)
Konosu-Fukaya S, Nakamura Y, Satoh F, Ono Y, Felizola SJ, Ise K, Maekawa T, Takeda K, Katsu K, Fujishima F, Kasajima A, Watanabe M, Arai Y, Gomez-Sanchez EP, Gomez-Sanchez CE, Doi M, Okamura H, and Sasano H
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Journal Title
Mol. Cell. Endocrinol.
Volume: 印刷中
Pages: 205-212
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Steroidogenic enzymes, their related transcription factors and nuclear receptors in human sebaceous glands under normal and pathological conditions2014
Author(s)
Azmahani A, Nakamura Y, Felizola SJ, Ozawa Y, Ise K, Inoue T, McNamara KM, Doi M, Okamura H, Zouboulis CC, Aiba S, and Sasano H
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Journal Title
J. Steroid Biochem. Mol. Biol.
Volume: 144
Pages: 268-279
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Isoform-specific monoclonal antibodies against 3beta-hydroxysteroid dehy drogenase/isomerase family provide markers for subclassification of hum an primary aldosteronism. .2014
Author(s)
Doi M, Satoh F, Maekawa T, N akamura Y, Fustin JM, Tainaka M, Hotta Y, Takahashi Y, Morimoto R, Takase K, Ito S, Sasano H, and Okamura H
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Journal Title
J Clin Endocrinol Metab
Volume: 99
Issue: 2
Pages: 257-62
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Immunolocalization of murine type VI 3β-hydroxysteroid dehydrogenase in the adrenal gland, testis, skin, and placenta2014
Author(s)
Koki Yamamura, Magao Doi, Hida Hayashi, Takumi Ota, Iori Murai, Yunhong Hotta, Rie Komatsu, Hitoshi Okamura
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Journal Title
Molecular and Cellular Endocrinology
Volume: 382
Issue: 1
Pages: 131-138
DOI
Related Report
Peer Reviewed
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