| Project/Area Number |
10470488
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Biological pharmacy
|
|---|
| Research Institution | Teikyo University |
|---|
Principal Investigator |
WAKU Keizo Faculty of Pharmaceutical Science, Teikyo University, Professor, 薬学部, 教授 (90013854)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KONDO Sachiko Faculty of Pharmaceutical Science, Teikyo University, Research Associate, 薬学部, 助手 (10286982)
KISHIMOTO Seishi Faculty of Pharmaceutical Science, Teikyo University, Research Associate, 薬学部, 助手 (60234217)
YAMASHITA Atsushi Faculty of Pharmaceutical Science, Teikyo University, Lecturer, 薬学部, 講師 (80230415)
|
|---|
| Project Period (FY) |
1998 – 1999
|
| Project Status |
Completed (Fiscal Year 1999)
|
| Budget Amount *help |
¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 1999: ¥4,800,000 (Direct Cost: ¥4,800,000)
|
|---|
| Keywords | cannabinoid / arachidonoylglycerol / monoglyceride / anadamide / arachidonic acid |
|---|
| Research Abstract |
We have found that 2-arachidonoylglycerol is the endogenous cannabinoid receptor ligand (CB1 receptor) in NG-108-15 cells and caused the transient increase in CaィイD12+ィエD1 concentration in the cells when 2-arachidonoylglycerol was added to the cell suspension. Twenty four structural analogs of 2-arachidonoylglycerol were prepared and tested the ability of rise of CaィイD12+ィエD1 in the cells. It was demonstrated that 2-arachidonoylglycerol was found to be the most potent compound after testing all of the compounds and the rise of CaィイD12+ィエD1 in the cells began as low as 0.3 nM of the compound. Whereas HU-210 and CP55940, the synthetic cannabinoid receptor agonists, raised the CaィイD12+ィエD1 at 0.3 nM,. The maximum rises of CaィイD12+ィエD1 were much lower than that of 2-arachidonoylglycerol. The above results clearly showed that 2-arachidonoylglycerol is the full agonist and real endogenous cannabinoid receptor ligand in the neuronal cells.
Next, we investigated the biosynthetic route of 2-arachidonoylglycerol in the brain. In the rat brain homogenate, 2-arachidonoylglycerol and diaylglycerol containing arachidonic acid was rapidly generated during incubation. When diaylglycerol containing arachidonic acid was added to the rat brain homogenate, 2-arachidonoylglycerol was detected. 2-Arachidonoylglycerol was produced from radioactive phosphatidylinositol, but not from phosphatidylcholine or phosphatidylethanolamine. These data strongly suggest that phosphatidylinositol was hydrolyzed to diacylglycerol by phospholipase C action and converted into 2-arachidonoylglycerol by diacylgllycerol lipase.
|
