2011 Fiscal Year Final Research Report
Molecular mechanism of persisting activation of glutamate-gated chloride channels by macrolide compounds
| Project/Area Number |
21310147
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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 |
Living organism molecular science
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| Research Institution | Kinki University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
OZOE Yoshihisa 島根大学, 生物資源科学部, 教授 (80112118)
OKAJIMA Toshihide 大阪大学, 産業科学研究所, 准教授 (10247968)
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| Co-Investigator(Renkei-kenkyūsha) |
YAMASHITA Atsuko 独立行政法人理化学研究所, 播磨研究所・分子シグナリング研究チーム, チームリーダー (10321738)
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| Project Period (FY) |
2009 – 2011
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| Keywords | マクロライド / イベルメクチン / ミルベマイシン / 抑制性グルタミン酸受容体 / 光親和性プローブ / 大量発現 / バインディングアッセイ / パッチクランプ |
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| Research Abstract |
This study was aimed at elucidating the mechanism of action of macrolide compounds ivermectin(IVM) and milbemycin(MLM) on glutamate gated chloride ion channels(GluCls). Several photoaffinity probes were synthesized and confirmed to be capable of inhibiting[H^3] MLM-A_4 binding to nematode and insect GluCls at nano molar concentrations. Meanwhile, silkworm GluCl(BmGluCl) structural features that influence the receptor amount were identified and a method to overexpress them in Sf9 cells was established. Further, some amino acids critical for the actions of MLM-A_4 on a nematode GluCl were identified and two possible MLM-A_4 binding sites in the receptor were proposed.
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