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首页> 外文期刊>Cellular Physiology and Biochemistry >α,β-DCP-LA selectively activates PKC-ε and stimulates neurotransmitter release with the highest potency among 4 diastereomers
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α,β-DCP-LA selectively activates PKC-ε and stimulates neurotransmitter release with the highest potency among 4 diastereomers

机译：α，β-DCP-LA选择性激活PKC-ε并刺激神经递质释放，这是4种非对映异构体中最高的

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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,β-, α,β-, α,β-, and α,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 ε7 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.
机译：背景/目的：我们一直在使用8- [2-（2-戊基-环丙基甲基）-环丙基]-辛酸（DCP-LA）探测生物活性，该化合物是具有环丙烷环而不是顺式-双键的亚油酸衍生物。外消旋修饰。外消旋DCP-LA可能包含4种非对映异构体。因此，我们分别合成了DCP-LA非对映异构体，例如α，β-，α，β-，α，β-和α，β-DCP-LA，并评估了每种非对映异构体对蛋白激酶C（PKC）活性的影响和发射器释放。方法：采用高效液相色谱（HPLC）系统测定无细胞条件下和PC-12细胞中的PKC活性，以及​​从大鼠脑切片中释放的谷氨酸，多巴胺和5-羟色胺。结果：在4种非对映异构体α，β-DCP-LA中，选择性和直接激活了PKC-ε，具有最高的效能。在PKC（可能是PKC-ε和α7烟碱型ACh受体）的控制下，α，β-DCP-LA分别刺激大鼠海马，纹状体和下丘脑片中谷氨酸，多巴胺和5-羟色胺的释放。 4个非对映异构体。结论：α，β-DCP-LA可作为PKC-ε的选择性直接活化剂，通过靶向ε7烟碱型ACh受体来刺激递质释放。这表明，α，β-DCP-LA可以作为一种有前途的药物开发，不仅可以治疗痴呆症，还可以治疗由于神经递质减少/缺乏而引起的神经退行性疾病和精神疾病。

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