Cynarin, a caffeoylquinic acid derivative in artichoke, inhibits exocytotic glutamate release from rat cortical nerve terminals (synaptosomes).

Autor: Lu CW; Department of Anesthesiology, Far-Eastern Memorial Hospital, New Taipei City, 22060, Taiwan; Department of Mechanical Engineering, Yuan Ze University, Taoyuan, 32003, Taiwan., Lin TY; Department of Anesthesiology, Far-Eastern Memorial Hospital, New Taipei City, 22060, Taiwan; Department of Mechanical Engineering, Yuan Ze University, Taoyuan, 32003, Taiwan., Hsieh PW; Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan City, Taiwan; Graduate Institute of Natural Products, School of Traditional Chinese Medicine, And Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, 33303, Taiwan., Chiu KM; Division of Cardiovascular Surgery, Cardiovascular Center, Far-Eastern Memorial Hospital, New Taipei City, 22060, Taiwan; Department of Electrical Engineering, Yuan Ze University, Taoyuan, 32003, Taiwan., Lee MY; Department of Medical Research, Far-Eastern Memorial Hospital, New Taipei, 22060, Taiwan., Wang SJ; Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan City, Taiwan; School of Medicine, Fu Jen Catholic University, New Taipei City, 24205, Taiwan. Electronic address: med0003@mail.fju.edu.tw.
Jazyk: angličtina
Zdroj: Neurochemistry international [Neurochem Int] 2023 Jul; Vol. 167, pp. 105537. Date of Electronic Publication: 2023 May 08.
DOI: 10.1016/j.neuint.2023.105537
Abstrakt: The purpose of this study was to evaluate the effect of cynarin, a caffeoylquinic acid derivative in artichoke, on glutamate release elicited by 4-aminopyridine (4-AP) in rat cortical nerve terminals (synaptosomes). We observed that cynarin decreased 4-aminopyridine-elicited glutamate release, which was prevented by the removal of external free Ca 2+ with ethylene glycol bis (β-aminoethyl ether)-N,N,N,N-tetraacetic acid (EGTA) or the blockade of P/Q-type calcium channels with ω-agatoxin IVA. Molecular docking also revealed that cynarin formed a hydrogen bond with the P/Q-type Ca 2+ channel, indicating a mechanism of action involving Ca 2+ influx inhibition. Additionally, the inhibitory effect of cynarin on glutamate release is associated with a change in the available synaptic vesicles, as cynarin decreased 4-AP-elicited FM1-43 release or hypertonic sucrose-evoked glutamate release from synaptosomes. Furthermore, the suppression of protein kinase A (PKA) prevented the effect of cynarin on 4-AP-elicited glutamate release. 4-AP-elicited PKA and synapsin I or synaptosomal-associated protein of 25 kDa (SNAP-25) phosphorylation at PKA-specific residues were also attenuated by cynarin. Our data indicate that cynarin, through the suppression of P/Q-type Ca 2+ channels, inhibits PKA activation and attenuates synapsin I and SNAP-25 phosphorylation at PKA-specific residues, thus decreasing synaptic vesicle availability and contributing to glutamate release inhibition in cerebral cortex terminals.
Competing Interests: Declaration of competing interest None.
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Databáze: MEDLINE