Chlorogenic Acid Decreases Glutamate Release from Rat Cortical Nerve Terminals by P/Q-Type Ca(2+) Channel Suppression: A Possible Neuroprotective Mechanism.
Chlorogenic Acid Decreases Glutamate Release from Rat Cortical Nerve Terminals by P/Q-Type Ca(2+) Channel Suppression: A Possible Neuroprotective Mechanism.
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DOI：
10.3390/ijms222111447
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发表时间：
2021-10-23
影响因子：
5.6
通讯作者：
Wang SJ
中科院分区：
文献类型：
--
作者：
Hung YC;Kuo YH;Hsieh PW;Hsieh TY;Kuo JR;Wang SJ
多巴胺能神经递质系统在神经系统疾病的病理生理学和治疗研究中受到了极大的关注。该研究探讨了多酚化合物绿原酸（CGA）对大鼠大脑皮质神经末梢（突触体）谷氨酸释放的影响。CGA抑制4-氨基吡啶（4-AP）诱导的突触体谷氨酸释放。这种抑制被阻止在细胞外Ca 2+的情况下，并与抑制4-AP诱导的Ca 2+升高，但不归因于突触体膜电位的变化。与通过分子对接观察到的证据一致，在P/Q型Ca 2+通道抑制剂存在下，CGA不抑制谷氨酸释放;因此，CGA诱导的谷氨酸释放抑制可能由P/Q型Ca 2+通道介导。钙调蛋白和钙调蛋白依赖性激酶II（Ca 2 +/CaMKII）抑制剂也减弱了CGA诱导的谷氨酸释放抑制，CGA降低了CaMKII及其底物突触蛋白I的磷酸化。此外，腹腔注射CGA预处理减轻红藻氨酸给药引起的大鼠皮层谷氨酸升高和神经元损伤。这些结果表明，CGA通过抑制P/Q-型Ca 2+通道和CaMK II/突触蛋白I通路来抑制皮层突触体的谷氨酸释放，从而防止对皮层神经元的兴奋性毒性损伤。
The glutamatergic neurotransmitter system has received substantial attention in research on the pathophysiology and treatment of neurological disorders. The study investigated the effect of the polyphenolic compound chlorogenic acid (CGA) on glutamate release in rat cerebrocortical nerve terminals (synaptosomes). CGA inhibited 4-aminopyridine (4-AP)-induced glutamate release from synaptosomes. This inhibition was prevented in the absence of extracellular Ca2+ and was associated with the inhibition of 4-AP-induced elevation of Ca2+ but was not attributed to changes in synaptosomal membrane potential. In line with evidence observed through molecular docking, CGA did not inhibit glutamate release in the presence of P/Q-type Ca2+ channel inhibitors; therefore, CGA-induced inhibition of glutamate release may be mediated by P/Q-type Ca2+ channels. CGA-induced inhibition of glutamate release was also diminished by the calmodulin and Ca2+/calmodilin-dependent kinase II (CaMKII) inhibitors, and CGA reduced the phosphorylation of CaMKII and its substrate, synapsin I. Furthermore, pretreatment with intraperitoneal CGA injection attenuated the glutamate increment and neuronal damage in the rat cortex that were induced by kainic acid administration. These results indicate that CGA inhibits glutamate release from cortical synaptosomes by suppressing P/Q-type Ca2+ channels and CaMKII/synapsin I pathways, thereby preventing excitotoxic damage to cortical neurons.
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影响因子：
4.8
作者：
Gao, Lijuan;Li, Xiaoqiong;Xu, Shijun
通讯作者：
Xu, Shijun
DOI：
10.1002/neu.480230915
发表时间：
1992-11-01
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
CHOI, DW
通讯作者：
CHOI, DW
影响因子：
5.5
作者：
LLINAS, R;GRUNER, JA;GREENGARD, P
通讯作者：
GREENGARD, P
影响因子：
3.5
作者：
COFFEY, ET;SIHRA, TS;POCOCK, JM
通讯作者：
POCOCK, JM
影响因子：
4.6
作者：
Lee, Tae-Kyeong;Kang, Il-Jun;Won, Moo-Ho
通讯作者：
Won, Moo-Ho