| Project/Area Number |
09670091
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
General pharmacology
|
|---|
| Research Institution | KOBE UNIVERSITY |
|---|
Principal Investigator |
SAITO Naoaki Kobe University, Biosignal Research Center, Professor, バイオシグナル研究センター, 教授 (60178499)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SAKAI Norio Kobe University, Biosignal Research Center, Assistant Professor, バイオシグナル研究センター, 助手 (70263407)
SHIRAI Yasuhito Kobe University, Biosignal Research Center, Assistant Professor, バイオシグナル研究センター, 助手 (60263399)
|
|---|
| Project Period (FY) |
1997 – 1998
|
| Project Status |
Completed (Fiscal Year 1998)
|
| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥2,400,000 (Direct Cost: ¥2,400,000)
|
|---|
| Keywords | serotonin / transporter / interferon / phosphorylation / depression / synapse / electron microscopy / 脱リン酸化 / 変異体 / COS-7細胞 |
|---|
| Research Abstract |
We examined the regulatory mechanism of serotonin transporter and the involvement of serotonin transporter (SET) in depression to elucidate the function role of SET in mental disorder.
1. Regulation of SET by phosphorylation. The regulation of SET expressed in COS7 cells by the activation of protein kinase C with phorbol ester or by inhibition of protein phosphatases with calyculin A was examined. Both treatment decreased the activity of SET with a reduction in Vmax without affecting Km. Site-directed mutagenesis of five putative PKC phosphorylation sites in SET revealed that these inhibitory modulation of SET activity did not act via direct phosphorylation of SET by PKC.
2. Immunocytochemical localization of SET.The cellular and intracellular localization of SET was examined by immunocytochemistry. SET was localized in the varicose nerve fibers and nerve terminals but not in the cell bodies. Under electron microscopy, SET was seen around the synaptic vesicles as well as presynaptic membrane.
3. The effects of interferon-alpha and -gamma on the transcription of SET.Both SET mRNA and SET activity were increased by treatment with interferon-alpha and -gamma for 3 h. Treatment with dibutyryl cAMP also increased SET mRNA and SET activity. The level of SET mRNA was increased both in the midbrain and adrenal glands of mice which were treated with interferons for 3 h. These results suggest that the interferon-induced psychiatric side effects arise through regulation of serotonin transporter transcription and that the transcriptional regulation of the serotonin transporter is a possible neurochemical mechanism of affective disorders.
|
