2002 Fiscal Year Final Research Report Summary
Exploration of endogenous novel ligands for glutamate receptors with a high sub-type specificities
| Project/Area Number |
13672277
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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 |
Biological pharmacy
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| Research Institution | Osaka Prefecture University (2002)
Kanazawa University (2001) |
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Principal Investigator |
NAKAMURA Yoichi Grad. School of Agriculture and Biological Sciences, Lab. of Integrative Physiology in Vet. Sciences, Professor, 大学院・農学生命科学研究科, 教授 (90180413)
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| Co-Investigator(Kenkyū-buntansha) |
YONEDA Yukio Kanazawa University Grad. School of Natural Science and Technology, Professor, 大学院・自然科学研究科, 教授 (50094454)
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| Project Period (FY) |
2001 – 2002
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| Keywords | D-aspartate / L-serine / glutamate / serine transporter / autoradiography / amino acid uptake / cerebellum / neuroactive amino acids |
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| Research Abstract |
In this research project we obtained two findings on the mechanism of central amino acids-signaling system as follows:
Expression specifically in cerebellum of glutamate transporters with stereo-selectivity - The Na^+-dependent, "high-affinity" transport of L-glutamate (GluT) in brain tissue has become a significant focus of interest, particularly since it has been revealed that abnormalities of GluT may be associated with serious neurological disorders. Using quantitative autaradiography, we have studied the distribution and pharmacology of radioligand binding to sites with characteristics of the substrate-recognition/binding locus on GluT. We have determined IC_<50> values for the inhibition of [^3H]L- and [^3H]D-Asp binding by their non-radioactive counterparts. The two radioligands did not appreciably differ from each other in then interactions with the binding sites in the forebrain, consistent with all Na^+-dependent GluT binding sites in that region having no stereo-selectivity f
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or aspartate enantiomers. In the cerebellar cortex, however, the data indicated the presence of a GluT binding site mat preferred L- over D-aspartate. These findings contrast with many previous in cerebellar cortex. A possibility of an existence of hitherto unknown molecules with properties of a glutamate transporter should be considered.
A novel L-serine transporters in central nervous system-It was reported that L-serine (Ser) induces postsynaptic inhibitory potentials; however, little is elucidated about the mechanism of its neuro-transmission. We found here a novel high affinity uptake activity for L-Ser in rat brain. A half of that is not dependent on Na^+ concentration and it was composed by more than two different transporters systems. Pharmacological characteristics of that was distinct from known amino acid transporters
According to these findings and other results in this research project, it is strongly suggested that D-Asp and L-Ser play a role for neuronal transmission beside classical neuroactive amino acids. Less
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