論文 - 詳細
| RRC ID | 18175 |
|---|---|
| 著者 | Shimizu T, Kanno T, Tanaka A, Nishizaki T. |
| タイトル | α, β-DCP-LA selectively activates PKC-ε and stimulates neurotransmitter release with the highest potency among 4 diastereomers. |
| ジャーナル | Cell Physiol Biochem |
| Abstract |
BACKGROUND/AIMS:We have been probing bioactivities of 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA), a linoleic acid derivative with cyclopropane rings instead of cis-double bonds, using a racemic modification. Racemic DCP-LA contains possible 4 diastereomers. We, therefore, separately synthesized DCP-LA diastereomers such as α α-, α, β-, β,α-, and β, β-DCP-LA and assessed the effects of each diastereomer on protein kinase C (PKC) activity and transmitter release. METHODS:PKC activity under the cell-free conditions and in PC-12 cells, and glutamate, dopamine, and serotonin released from rat brain slices were assayed with a high performance liquid chromatography (HPLC) system. RESULTS:Of 4 diastereomers α, β-DCP-LA selectively and directly activated PKC-e, with the highest potency. α β-DCP-LA stimulated release of glutamate, dopamine, and serotonin from rat hippocampal, striatal, and hypothalamic slices, respectively, under the control of PKC, possibly PKC-e, and α7 nicotinic ACh receptors, with the highest potency among 4 diastereomers. CONCLUSION:α, β-DCP-LA serves as a selective and direct activator of PKC-e, to stimulate transmitter release by targeting α7 nicotinic ACh receptors. This suggests that α, β-DCP-LA could be developed as a promising drug for treatment of not only dementia but neurodegenerative diseases and psychiatric disorders due to reduction/deficiency of neurotransmitters. |
| 巻・号 | 27(2) |
| ページ | 149-58 |
| 公開日 | 2011-1-1 |
| DOI | 10.1159/000325217 |
| PII | 000325217 |
| PMID | 21325832 |
| MeSH | Animals Brain / metabolism Caprylates / chemistry Caprylates / pharmacology* Dopamine / metabolism* Glutamic Acid / metabolism* PC12 Cells Protein Kinase C-epsilon / genetics Protein Kinase C-epsilon / metabolism* RNA Interference RNA, Small Interfering / metabolism Rats Receptors, Nicotinic / metabolism Serotonin / metabolism* Stereoisomerism alpha7 Nicotinic Acetylcholine Receptor |
| IF | 5.5 |
| 引用数 | 20 |
| WOS 分野 | PHYSIOLOGY CELL BIOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | PC-12(RCB0009) |