| Project/Area Number |
07457024
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
General pharmacology
|
|---|
| Research Institution | Kansai Medical University |
|---|
Principal Investigator |
INAGAKI Chiyoko Kansai Medical University, Professor, 医学部, 教授 (60025640)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KITAGAWA Kaori Kansai Medical University, Research Associate, 医学部, 助手 (10165813)
HATTORI Naoki Kansai Medical University, Research Associate, 医学部, 助手 (80288828)
OTANI Hitomi Kansai Medical University, Research Associate, 医学部, 助手 (40140272)
HARA Mitsuyoshi Kansai Medical University, Assistant Professor, 医学部, 講師 (50192282)
OMORI Kyoko Kansai Medical University, Associate Professor, 医学部, 助教授 (90152256)
TANABE Takatoshi Kansai Medical University, Research Associate (50268356)
MIKAMI Toshiko Kansai Medical University, Research Associate (40203608)
|
|---|
| Project Period (FY) |
1995 – 1996
|
| Project Status |
Completed (Fiscal Year 1996)
|
| Budget Amount *help |
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1996: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1995: ¥4,900,000 (Direct Cost: ¥4,900,000)
|
|---|
| Keywords | chloride ion / signal transduction / c-fos expression / G-protein / beta-adrenoceptor / metabotropic glutamate receptor / inositol phosphate / chloride pump / 細胞内塩素イオン濃度 / カテコラミンβ受容体 / G蛋白 / サイクリックAMP / イノシトール三リン酸 |
|---|
| Research Abstract |
1. Roles of intracellular Cl^- concentration ( [Cl^-] _i) in c-fos expression in the brain.
Intracerebroventricular injection of ethacrynic acid that inhibits neuronal Cl^- extrusion and induces glutamate release, increased c-fos expression in hippocampal neurons in mice. Analyzes of the time courses by Northern blot and in situ hybridization showed two peaks of c-fos mRNA levels 60 min and 10-14 days after the injection of ethacrynic acid. In parallel with the time couses, levels of nerve growth factor mRNA also increased in the same brain regions.
2. Roles of [Cl^-] _i in responses to beta-adrenoceptor stimulation.
Adrenoceptor-mediated Cl^- transport in cultured rabbit corneal endothelium was examined using a Cl^--sensitive fluorescent dye. The corneal endothelial cells accumulated Cl^<> upon beta-adrenoceptor stimulation under the condition of low [Cl^-] _i (<30mM), but not under the conditions of [Cl^-] _i<greater than or equal>30mM,probably via acceleration of G-protein subunit dissociation followed by activation of cAMP-dependent proteinkinase and Na^+/K^+/Cl^- cotransporter.
3. Role of [Cl^-] _i in responses to metabotropic glutamate receptor (mGluR) stimulation.
When [Cl^-] _i was changed, stimulation of mGluRl alpha expressed in Chinese hamster ovary cells yielded different amounts of IP_3 with a peak at 20mM of [Cl^-] _i. Pertussis toxin (PTX) blocked the [Cl^-] _i-sensitive IP_3 formation suggesting that activation of mGluR-coupled PTX-sensitive G-protein is sensitive to [Cl^-] _i.
4. A new [Cl^-] _i regulating system.
Neuronal outwardly directed Cl^- transport system (Cl^- pump) was identified as 520 kDa protein that primarily transports Cl^- in an ATP-dependent manner to lower neuronal [Cl^-] _i when reconstituted in liposomes.
|
