| Project/Area Number |
12470500
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | OKAYAMA UNIVERSITY |
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Principal Investigator |
MORIYAMA Yoshinori OKAYAMA UNIVERSITY Graduate School of Natural Science and Technology, professor, 大学院・自然科学研究科, 教授 (10150658)
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| Co-Investigator(Kenkyū-buntansha) |
OTSUKA Masato OKAYAMA UNIVERSITY, Faculty of Pharmaceutical Sciences, assistant, 薬学部, 助手 (30243489)
TSUBOI Seiji OKAYAMA UNIVERSITY Graduate School of Natural Science and Technology, associate professor, 大学院・自然科学研究科, 助教授 (50172052)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 2002: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2001: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | melatonin / circadyan rhythm / pineabcyte / glutamate / receptor / aspartate / serotonin-N-acetyltransferase(NAT) / serotonin / マイクロベジクル / 松果体細胞 / 小胞型グルタミン酸輸送体 / N-actyltranferase / 結晶化 / Dアスパラギン酸 / シナプス小胞 |
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| Research Abstract |
Pineal gland converts time signals from SCN to hormonal signals : pinealocytes synthesize melatonin as a circadyan rhythm hormone, and secrete it through blood stream. Serotonin N-acetyltransferase (SNAT) plays a sentral role for synthesis of melatonin, and thus, its activities are definitly controlled through several pathways. In the research project, we found two distinct novel regulatory mechanisms for SNAT regulation : [I] L-glutamate-mediated autonomic regulation, and [II] intramolecular regulation through cleavage of disulfide bond. The summary of each systems are as follows :
[I] Overall characteristics of the L-glutamate-mediated autonomic regulatory system. We found that pinealocytes are glutamatergic. The cells store L-glutamate in synaptic-like microvesicles and secrete it through exocytosis. The released glutamate is involved in negative regulation of melatonin synthesis. We have identified and characterized various receptors and transporters involving in the processes. We have solved the molecular mechanism of L-glutamate secretion.
[II] The mechanism of intramolecular regulation of SNAT. We found that SNAT showed two forms (active and inactive state) through exchange of -S-S- to -SH and HS-. We identified two systein residues incolving the processes. We found that this regulation also occurs under physiological conditions, and play a central role in SNAT regulation.
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