Plantainoside D Reduces Depolarization-Evoked Glutamate Release from Rat Cerebral Cortical Synaptosomes

• Published in: Molecules (Basel, Switzerland) Vol. 28; no. 3; p. 1313
• Main Authors: Chiu, Kuan-Ming, Lee, Ming-Yi, Lu, Cheng-Wei, Lin, Tzu-Yu, Wang, Su-Jane
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 30.01.2023; MDPI
• Subjects: 4-Aminopyridine - pharmacology; Alzheimer's disease; Analysis; Animals; Calcium - metabolism; Calcium Channel Blockers - pharmacology; Calcium ions; Calcium Signaling; cerebral cortex; Cerebral Cortex - metabolism; Enzymes; glutamate release; Glutamic Acid - metabolism; Health aspects; Homeostasis; Kinases; Neurophysiology; Neurotransmitters; Oxidative stress; Parkinson's disease; PKC; plantainoside D; Properties; Protein Kinase C - metabolism; Protein kinases; Proteins; Rats; Rats, Sprague-Dawley; synaptosomes; Synaptosomes - metabolism; voltage-dependent Ca2+ channel; Taiwan; voltage-dependent Ca2+ channel; cerebral cortex; PKC; plantainoside D; synaptosomes; glutamate release
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules28031313

Inhibiting the excessive release of glutamate in the brain is emerging as a promising therapeutic option and is efficient for treating neurodegenerative disorders. The aim of this study is to investigate the effect and mechanism of plantainoside D (PD), a phenylenthanoid glycoside isolated from Plantago asiatica L., on glutamate release in rat cerebral cortical nerve terminals (synaptosomes). We observed that PD inhibited the potassium channel blocker 4-aminopyridine (4-AP)-evoked release of glutamate and elevated concentration of cytosolic Ca2+. Using bafilomycin A1 to block glutamate uptake into synaptic vesicles and EDTA to chelate extracellular Ca2+, the inhibitory effect of PD on 4-AP-evoked glutamate release was prevented. In contrast, the action of PD on the 4-AP-evoked release of glutamate in the presence of dl-TBOA, a potent nontransportable inhibitor of glutamate transporters, was unaffected. PD does not alter the 4-AP-mediated depolarization of the synaptosomal membrane potential, suggesting that the inhibitory effect of PD on glutamate release is associated with voltage-dependent Ca2+ channels (VDCCs) but not the modulation of plasma membrane potential. Pretreatment with the Ca2+ channel blocker (N-type) ω-conotoxin GVIA abolished the inhibitory effect of PD on the evoked glutamate release, as did pretreatment with the protein kinase C inhibitor GF109203x. However, the PD-mediated inhibition of glutamate release was eliminated by applying the mitochondrial Na+/Ca2+ exchanger inhibitor CGP37157 or dantrolene, which inhibits Ca2+ release through ryanodine receptor channels. These data suggest that PD mediates the inhibition of evoked glutamate release from synaptosomes primarily by reducing the influx of Ca2+ through N-type Ca2+ channels, subsequently reducing the protein kinase C cascade.