1995 Fiscal Year Final Research Report Summary
Screening of drugs for neurodegenerative disorders using neurotransmitter release machinery expressed in Xenopus oocytes
| Project/Area Number |
05557010
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
General pharmacology
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| Research Institution | Kobe University |
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Principal Investigator |
SHUNTOH Hisato Kobe University School of Medicine Associate Professor Faculty of Health Science, 医学部, 助教授 (70206259)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Naoaki Kobe University, Biosignal Res.Center Dept.Mol.pharmacol.Professor, バイオシグナル研究センター, 教授 (60178499)
KUNO Takayoshi Kobe University School of Medicine Dept.pharmacol.Professor, 医学部, 教授 (50144564)
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| Project Period (FY) |
1993 – 1995
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| Keywords | Calcineurin / GABA transporter / Long-term potentiation / FK506 / Adaptin / Lipid kinase / Endocytosis / Neural visinin-like calcium-binding proteins |
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| Research Abstract |
1. Complementary DNA clones encoding neural visinin-like calcium-binding proteins (NVP-1, NVP-2 and NVP-3) were isolated from rat brain cDNA library. NVP-1, NVP-2 and NVP-3 mRNAs are most highly expressed in brain and are differentially expressed in various regions of rat brain. Furthermore, alterations in NVP-1 may be involvedin the pathology of Phecyclidine-induced psychosis. 2. The effect of phorbol ester on the Na+-dependent uptake of GABA by rat cortical synaptosomes and Xenopus oocytes expressing GAT1 (neuronal GABA transporter) was examined. Protein kinase C may modulate the GABA uptake into presynaptic terminals through the inhibition of GAT1 activity. 3. The serotonin release from RBL-2H3 cells is subject to tonic, Ca2+-independent, inhibition by protein phosphatase 1.4. In the Schaffer collateral-CA1 pathway in rat hippocampal slices, calyculin A induced a long-lasting potentiation of the extracellularfield potentials with a transient increase in glutamate release. 5. Heat shock transiently suppresses the inositol trisphosphate-mediated intracellular calcium signal transduction system and that HSP72 is involved in the recovery of receptor-stimulated calcium rise in the neuronal cells. 6. By screening the mutagen-treated fission yeast cells, immunosuppressant- and temperature- sensitive (its1-6) mutant strains were isolated. Gene products of its1+ and its3+ were beta-adaptin homolog, which is a subunit of adapter protein AP-2, and Pl (4) P5-kinase homolog, which is required for exocytosis, respectively. These results suggest that calcineurin plays an important role in vesicular recycling. In conclusion, our several results provide important clues about the molecular basis of neurotransmitter release and secretory vesicle recycling or endocytosis.
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