α, β-DCP-LA Selectively Activates PKC-ε and Stimulates Neurotransmitter Release with the Highest Potency among 4 Diastereomers

Cellular Physiology and Biochemistry

关键词: DCP-LA;    Diastereomer;    Selective optical resolution;    PKC-ε;    Transmitter release;   

DOI  :  10.1159/000325217

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

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-ε, 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-ε, 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-ε, 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.

【 授权许可】

CC BY-NC-ND