title: Xanthohumol-induced presynaptic reduction of glutamate release in the rat hippocampus.
abstract: This study examined whether xanthohumol, a hop-derived prenylated flavonoid present in beer, affects glutamate release in the rat hippocampus. In the rat hippocampal nerve terminals (synaptosomes), xanthohumol inhibited the release of 4-aminopyridine (4-AP)-evoked glutamate and the elevation of cytosolic Ca(2+) concentration, whereas it had no effect on 4-AP-mediated depolarization. The inhibitory effect of xanthohumol on the evoked glutamate release was prevented by removing extracellular Ca(2+), using the Cav2.2 (N-type) and Cav2.1 (P/Q-type) channel blocker ω-CgTX MVIIC, the calmodulin antagonists W7 and calmidazolium, and the protein kinase A inhibitor H89; however, no such effect was observed when the G-protein inhibitor N-ethylmaleimide was used. In addition, immunocytochemical data demonstrated that GABAA receptors are present in the hippocampal synaptosomes and that the xanthohumol effect on evoked glutamate release was antagonized by the GABAA receptor antagonist SR95531. Furthermore, in slice preparations, xanthohumol reduced the frequency of miniature excitatory postsynaptic currents without affecting their amplitude. We conclude that xanthohumol acts at GABAA receptors present in the hippocampal nerve terminals to decrease the Ca(2+) influx through N- and P/Q-type Ca(2+) channels, which subsequently suppresses the Ca(2+)-calmodulin/PKA cascade to decrease the evoked glutamate release.
authors.affiliation: School of Medicine, Fu Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Dist., New Taipei City, Taiwan 24205 and Department of Anesthesiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan111.
authors.forename: Yi
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei City, Taiwan 22060 and 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, Taiwan 22060 and Department of Mechanical Engineering, Yuan Ze University, Taoyuan 320, Taiwan.
authors.forename: Cheng Wei
authors.initials: CW
authors.lastname: Lu
authors.affiliation: Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei City, Taiwan 22060.
authors.forename: Shu Kuei
authors.initials: SK
authors.lastname: Huang
authors.affiliation: Department of Clinical Psychology, Fu Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Dist., New Taipei City, Taiwan 24205.
authors.forename: Ying Chou
authors.initials: YC
authors.lastname: Wang
authors.affiliation: School of Medicine, Fu Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Dist., New Taipei City, Taiwan 24205 and Graduate Institute of Basic Medicine, Fu Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Dist., New Taipei City, Taiwan 24205. med0003@mail.fju.edu.tw.
authors.forename: Su Jane
authors.initials: SJ
authors.lastname: Wang
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001515:Beer / Q000032:analysis; D002118:Calcium / Q000032:analysis / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D005419:Flavonoids / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism / Q000648:ultrastructure*; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D011427:Propiophenones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology; D013574:Synaptosomes / Q000737:chemistry / Q000502:physiology
chemical_list: D002121:Calcium Channel Blockers; D002147:Calmodulin; D005419:Flavonoids; D058787:GABA-A Receptor Antagonists; D007093:Imidazoles; D011427:Propiophenones; D011963:Receptors, GABA-A; D018698:Glutamic Acid; C031938:calmidazolium; D015761:4-Aminopyridine; D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium; C104536:xanthohumol