Analysis of the NMDA receptor-PDZ containing complexes as the drug targets
| Project/Area Number |
16590194
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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 |
General pharmacology
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| Research Institution | Yamaguchi University |
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Principal Investigator |
YAMADA Yasue Yamaguchi University, School of Medicine, Assistant professor, 医学部, 講師 (00166737)
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| Co-Investigator(Kenkyū-buntansha) |
INUI Makoto Yamaguchi University, School of Medicine, Professor, 医学部, 教授 (70223237)
KIMURA Yoshihiro Yamaguchi University, School of Medicine, Associate professor, 医学部, 助教授 (90301308)
KO Ji-Ai Yamaguchi University, School of Medicine, Assistant professor, 医学部, 講師 (70314797)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | NMDA receptor / PSD-95 / GKAP / PDZ / PKC / Src / oocyte / oocyte / MAGUKs |
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| Research Abstract |
We characterized the complex of NMDA receptor and PSD-95 using Xenopus oocyte expression system.
1.We examined the effects of PSD-95 and GKAP (guanylate kinase associated protein) on four different subtypes of the NMDA receptor. The complex of PSD-95 and GKAP potentiated the channel activity of NR1/NR2B, and NR1/NR2C, but not of NR1/NR2A and NR1/NR2D. The inhibitions of PKC-mediated potentiation of the channel activity of NR1/NR2A and NR1/NR2B were not influenced by co-expressing GKAP. These results indicate that PSD-95 and GKAP differently modulate the channel activity of four subtypes of the NMDA receptor.
2.SAP102, which is the member of MAGUKs family and PDZ containing protein, potentiated the basal channel activity of the NR1/NR2A and NR1/NR2B receptors. SAP102 inhibited the potentiation of the NR1/NR2A and NR1/NR2B channel activity induced by PKC. SAP102 also inhibited the Src-mediated potentiation of NR1/NR2A channels. Thus, SAP102 showed the similar effects to PSD-95 on NR1/NR2A-subtype NMDA receptor channels. The extent of the modulation by SAP102 was, however, lesser than that by PSD-95. These results indicate that the MAGUKs family modulates the NMDA receptor in a different manner.
3.We examined the effect of MK-801 and ketamine on oocytes expressing NR1/NR2A receptor and co-expressing with PSD-95. The NR1/NR2A receptor-PSD-95 complex showed the higher sensitivity to MK-801 and ketamine than the receptor alone. These results indicate that the receptor-PDZ-containing protein complex is a potential target to develop a new drug.
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Report
(3 results)
Research Products
(14 results)
