title: Apigenin, a natural flavonoid, inhibits glutamate release in the rat hippocampus.
abstract: The purpose of this study was to examine the effect and mechanism of apigenin, a natural flavonoid, on glutamate release in the rat hippocampus. In rat hippocampal nerve terminals (synaptosomes), apigenin inhibited glutamate release and the elevation of the cytosolic free Ca(2+) concentration evoked by 4-aminopyridine, whereas it had no effect on 4-aminopyridine-mediated depolarization and Na(+) influx. The apigenin-mediated inhibition of evoked glutamate release was prevented by chelating the extracellular Ca(2+) ions and blocking Cav2.2 (N-type) and Cav2.1 (P/Q-type) channel activity. Furthermore, we determined that gamma-aminobutyric acid type A (GABAA) receptors are present in the hippocampal nerve terminals because they are colocalized with the presynaptic marker synaptophysin. However, the effect of apigenin on 4-aminopyridine-evoked glutamate release from synaptosomes was unaffected by the GABAA receptor antagonists SR95531 and bicuculline. Furthermore, in slice preparations, whole-cell patch-clamp experiments showed that apigenin reduced the frequency of spontaneous excitatory postsynaptic currents without affecting their amplitude, suggesting a presynaptic mechanism. On the basis of these results, we suggested that apigenin exerts its presynaptic inhibition probably by reducing Ca(2+) entry mediated by the Cav2.2 (N-type) and Cav2.1 (P/Q-type) channels, thereby inhibiting glutamate release from the rat hippocampal nerve terminals.
authors.affiliation: Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei City 22060, Taiwan; Department of Chemistry, Fu Jen Catholic University, No. 510, Zhongzheng Road, Xinzhuang District, New Taipei City 24205, Taiwan.
authors.forename: Chia Ying
authors.initials: CY
authors.lastname: Chang
authors.affiliation: Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei City 22060, Taiwan; Department of Mechanical Engineering, Yuan Ze University, Taoyuan 320, Taiwan.
authors.forename: Tzu Yu
authors.initials: TY
authors.lastname: Lin
authors.affiliation: Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei City 22060, Taiwan; Department of Mechanical Engineering, Yuan Ze University, Taoyuan 320, Taiwan.
authors.forename: Cheng Wei
authors.initials: CW
authors.lastname: Lu
authors.affiliation: School of Medicine, Fu Jen Catholic University, No. 510, Zhongzheng Road, Xinzhuang District, New Taipei City 24205, Taiwan.
authors.forename: Chia Chuan
authors.initials: CC
authors.lastname: Wang
authors.affiliation: Department of Clinical Psychology, Fu Jen Catholic University, No. 510, Zhongzheng Road, Xinzhuang District, New Taipei City 24205, Taiwan.
authors.forename: Ying Chou
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Department of Chemistry, Fu Jen Catholic University, No. 510, Zhongzheng Road, Xinzhuang District, New Taipei City 24205, Taiwan.
authors.forename: Shang Shing Peter
authors.initials: SS
authors.lastname: Chou
authors.affiliation: Graduate Institute of Basic Medicine, Fu Jen Catholic University, No. 510, Zhongzheng Road, Xinzhuang District, New Taipei City 24205, Taiwan. Electronic address: med0003@mail.fju.edu.tw.
authors.forename: Su Jane
authors.initials: SJ
authors.lastname: Wang
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D047310:Apigenin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D011963:Receptors, GABA-A; D018698:Glutamic Acid; D047310:Apigenin; D012964:Sodium; D015761:4-Aminopyridine; D002118:Calcium
keywords: Apigenin; Glutamate release; Hippocampal slices; Hippocampal synaptosomes; Voltage-dependent Ca(2+) channels; sEPSCs