| Project/Area Number |
11680756
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
KITAYAMA Shigeo Hirosima University, Faculty of Dentistry, associate professor, 歯学部, 助教授 (80177873)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2000: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1999: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | norepinephrine / transporter / neurotransmitter / alternative splicing / antidipressant / 抗ラフ薬 / 抗うつ薬 |
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| Research Abstract |
We have identified rat norepinephrine transporter (NET) isoforms produced by alternative RNA splicing, designated rNETa and rNETb, latter of which was dominant negative when expressed with rNETa. To explore the role of RNA processing in regulation of NET expression, we analyzed the relationship between NET mRNA expression and norepinephrine (NE) transport in PC12 cells which are known to express NET.We isolated 12 different cell lines of PC12 which reveal different degrees of NE transport and NETb mRNA levels, however, there was no correlation between these. On the other hand, there was relation between total NET mRNA levels including both rNETa and rNETb and NE transport, suggesting the importance of the transcriptional regulation in NET functional expression. Next, we cloned rat NET gene at 3'-region, and transfected different cell lines with the expression vector carrying this clone. The transcripts observed in these cell lines derived from the introduced minigene were both rNETa and rNETb. These results suggest that regulation of NET expression resulted from species-specific splicing of NET pre-mRNA is mainly based on the differences in nucleotide sequences at the regions involved in splicing between species.
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