| Project/Area Number |
07457022
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
General pharmacology
|
|---|
| Research Institution | Sapporo Medical University |
|---|
Principal Investigator |
OHSHIKA Hideyo Sapporo Medical University School of Medicine Department of Pharmacology, Professor., 医学部, 教授 (50045358)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MIYAMOTO Atsushi Sapporo Medical University School of Medicine Department of Pharmacology, Associ, 医学部, 助教授 (50166196)
|
|---|
| Project Period (FY) |
1995 – 1996
|
| Project Status |
Completed (Fiscal Year 1996)
|
| Budget Amount *help |
¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 1996: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1995: ¥2,800,000 (Direct Cost: ¥2,800,000)
|
|---|
| Keywords | Signal transduction / Phospholipase C isoenzyme / G protein-mediated pathway / Dual regulation / Rat cerebral cortex / Gelsolin / Mouse neuroblastoma cells / ホスホリパーゼCアイソエンザイム / ホスホリパーゼC / イノシトールシリン酸 / Gタンパク質 / 受容体 / 高感受性 / 脱感受性 |
|---|
| Research Abstract |
Activation of phospholipase C (PLC) isoenzyme families through a G protein-mediated pathway has been widely indicated in many different cells and tissues. Whereas evidence for a G protein-dependent stimulation of PLC is abundant, reports on the inhibition of PLC through a G protein-mediated pathway have only recently started appearing. Moreover, it has been demonstrated that gelsolin (actin regulatory protein) has phosphatidylinositol (PtdIns) binding regions and has to be activated by Ca^<2+>. Although gelsolin is ubiquitous in normal mammalian tissues, relatively little is known about the role in neurological PtdIns-PLC systems. The present studies demonstrated (1) that rat cerebral-cortical membrane preparations retain G proteindependent inhibition of PLC activity and (2) the effect of gelsolin overexprssion on epidermal growth factor (EGF) receptor stimulation that mediates inositol 1,4,5-trisphosphate (IP_3) production in mouse neuroblastoma TBJ cells. Two diversity of functions a
… More
re attributed to PLC isozymes : 1) Our results indicate that nanomolar concentrations of guanine nucleotides in cerebral-cortical membranes promoted an inhibition of PLC activity and suggested that there may be dual effects of guanine nucleotides on the PLC system. Cerebral cortex membranes expressed a greater amount of PLC-beta_1 isoenzymes. Since PLC-beta_1 is the sffector for the G protein-mediated pathway, our studies suggest that the different G proteins regulate PLC activity through a shared mechanism that remains to be identified ; and 2) Gelsolim expression was increased in gelsolintransfected cells compared with controls, but PLC-beta_1, PLC-gamma_1 and PLC-delta_1 expression remained unchanged. No significant difference in the basal IP_3 production was observed between the groups. IP_3 production after stimulation with EGF was higher in gelsolin-transfected cells compared with controls. These result suggest that neurological gelsolin may play an important role in the PtcIns-PLC regulation systems. Less
|
