Chlorogenic Acid Decreases Glutamate Release from Rat Cortical Nerve Terminals by P/Q-Type Ca2+ Channel Suppression: A Possible Neuroprotective Mechanism

Autor: Yi-Chieh Hung, Pei-Wen Hsieh, Ting-Yang Hsieh, Su-Jane Wang, Yi-Hsiu Kuo, Jinn-Rung Kuo
Rok vydání: 2021
Předmět:
Male
Pharmacology
Membrane Potentials
Rats
Sprague-Dawley
chemistry.chemical_compound
Biology (General)
Neurotransmitter
synaptosome
Spectroscopy
Neurons
Synaptosome
CaMKII
Glutamate receptor
General Medicine
Computer Science Applications
Molecular Docking Simulation
Chemistry
Neuroprotective Agents
P/Q-type Ca2+ channel
cerebral cortex
neuroprotection
Synaptic Vesicles
endocrine system
Synapsin I
Kainic acid
QH301-705.5
chlorogenic acid
Glutamic Acid
Neuroprotection
Article
Catalysis
Calcium Channels
Q-Type
Inorganic Chemistry
Glutamatergic
Calmodulin
Ca2+/calmodulin-dependent protein kinase
glutamate release
Animals
Excitatory Amino Acid Agents
Physical and Theoretical Chemistry
QD1-999
Molecular Biology
Organic Chemistry
Calcium Channels
P-Type
Rats
chemistry
Synapses
Calcium
Calcium Channels
Calcium-Calmodulin-Dependent Protein Kinase Type 2
kainic acid
Synaptosomes
Zdroj: International Journal of Molecular Sciences
Volume 22
Issue 21
International Journal of Molecular Sciences, Vol 22, Iss 11447, p 11447 (2021)
ISSN: 1422-0067
DOI: 10.3390/ijms222111447
Popis: 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.
Databáze: OpenAIRE
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