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Plantainoside D Reduces Depolarization-Evoked Glutamate Release from Rat Cerebral Cortical Synaptosomes
oleh: Kuan-Ming Chiu, Ming-Yi Lee, Cheng-Wei Lu, Tzu-Yu Lin, Su-Jane Wang
Format: | Article |
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Diterbitkan: | MDPI AG 2023-01-01 |
Deskripsi
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 <i>Plantago asiatica</i> 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 Ca<sup>2+</sup>. Using bafilomycin A1 to block glutamate uptake into synaptic vesicles and EDTA to chelate extracellular Ca<sup>2+</sup>, 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 <span style="font-variant: small-caps;">dl</span>-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 Ca<sup>2+</sup> channels (VDCCs) but not the modulation of plasma membrane potential. Pretreatment with the Ca<sup>2+</sup> 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<sup>+</sup>/Ca<sup>2+</sup> exchanger inhibitor CGP37157 or dantrolene, which inhibits Ca<sup>2+</sup> 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 Ca<sup>2+</sup> through N-type Ca<sup>2+</sup> channels, subsequently reducing the protein kinase C cascade.