Chlorogenic Acid Decreases Glutamate Release from Rat Cortical Nerve Terminals by P/Q-Type Ca<sup>2+</sup> Channel Suppression: A Possible Neuroprotective Mechanism
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 (...
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| Autores principales: | , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/d0487f8944dc40f2958e1e6fde8450ae |
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| Sumario: | 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 Ca<sup>2+</sup> and was associated with the inhibition of 4-AP-induced elevation of Ca<sup>2+</sup> 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 Ca<sup>2+</sup> channel inhibitors; therefore, CGA-induced inhibition of glutamate release may be mediated by P/Q-type Ca<sup>2+</sup> channels. CGA-induced inhibition of glutamate release was also diminished by the calmodulin and Ca<sup>2+</sup>/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 Ca<sup>2+</sup> channels and CaMKII/synapsin I pathways, thereby preventing excitotoxic damage to cortical neurons. |
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