| Project/Area Number |
10480233
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B).
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
神経・脳内生理学
|
|---|
| Research Institution | Tokyo Medical and Dental Inversity graduate School (2000)
Tokyo Metropolitan Organization for Medical Research (1999)
Tokyo Metropolitan Institute for Neuroscience (1998) |
|---|
Principal Investigator |
KUBO Yoshihiro Tokyo Medical and Dental University Graduate School Department of Physiology, Professor, 大学院・医歯学総合研究科, 教授 (80211887)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MIWA Akiko Tokyo Metropolitan Institute for Neuroscience Dept.Molecular Physiology, Research Scientist, 東京都神経科学総合研究所, 主事研究員 (60142155)
OKADO Haruo Tokyo Metropolitan Institute for Neuroscience Dept.Molecular Physiology, Senior Research Scientist, 東京都神経科学総合研究所, 副参事研究員 (60221842)
MIYASHITA Tomoyuki Tokyo Metropolitan Institute for Neuroscience Dept.Molecular Physiology, Research Scientist, 東京都神経科学総合研究所, 主事研究員 (70270668)
|
|---|
| Project Period (FY) |
1998 – 2000
|
| Project Status |
Completed (Fiscal Year 2000)
|
| Budget Amount *help |
¥12,100,000 (Direct Cost: ¥12,100,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1999: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1998: ¥8,200,000 (Direct Cost: ¥8,200,000)
|
|---|
| Keywords | metabotropic / glutamate / receptor / calcium / cAMP / グルタミン酸受容体 / カルシウム / cAMP / metabotropic / glutamate / recceptor / calcium / sensing |
|---|
| Research Abstract |
We previously reported that the metabotropic glutamate receptor R1 a (mGluR1 α) can be activated not only by applying glutamate but also by raising extracellular Ca^<2+> (Ca^<2+>_0) concentration, and that the constant stimulation by Ca^<2+>_0 causes morphological change of transfected Chinese Hamster Ovary (CHO) cells. The physiological role of the Ca^<2+>_0-sensing function of mGluR1 α, however, is not fully clear yet, especially because Ca^<2+> is constitutively present an the extracellular space unlike other neurotransmitters. In this work, we aimed to elucidate the physiological significance of the Ca^<2+>_0-sensing function of mGluR1 α. The effect of mGluR1 α activation by Ca^<2+>_0on the morphological change of CHO cells was mimicked by forskolin. The effect of mGluR1 a activation on the morphological change was suppressed by the inhibitors of adenylate cyclase, protein kinase A (PKA) and MAP kinase kinase (MAPKK), and the effect of forskolin was also decreased by the inhibitors of PKA and MAPKK.These results demonstrate the involvement of cAMP, PKA, MAPKK, MARK pathway in the morphological change. We actually confirmed that the Ca^<2+>_0stimulation of mGluR1 α increased the basal cAMP level of transfected CHO cells. This increase in cAMP was observed even when only the membrane fraction of mGluR1 a transfected CHO cells were used, and the increase was inhibited by anti-Gsα antibody. Taken together, we concl uded that the Ca^<2+>_0-sensing function of mGluR1 a and the continuous stimulation by Ca^<2+>_0 caused the increase in the basal cAMP level by direct coupling with Gs, and triggered the subsequent activation of PKA, MAPKK, and MAPK cascade which resulted in the morphological change of transfected CHO cells.
|
