Xanthohumol-induced presynaptic reduction of glutamate release in the rat hippocampus
Autor: | Cheng Wei Lu, Ying Chou Wang, Yi Chang, Tzu Yu Lin, Su-Jane Wang, Shu Kuei Huang |
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Rok vydání: | 2015 |
Předmět: |
0301 basic medicine
Male Calmodulin Presynaptic Terminals Glutamic Acid Pharmacology Hippocampal formation Hippocampus Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Animals Channel blocker GABA-A Receptor Antagonists 4-Aminopyridine Flavonoids Propiophenones biology GABAA receptor Glutamate receptor Imidazoles Beer Depolarization General Medicine Calcium Channel Blockers Receptors GABA-A Cyclic AMP-Dependent Protein Kinases Rats 030104 developmental biology chemistry Biochemistry Xanthohumol Excitatory postsynaptic potential biology.protein Calcium 030217 neurology & neurosurgery Food Science Synaptosomes |
Zdroj: | Foodfunction. 7(1) |
ISSN: | 2042-650X |
Popis: | 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. |
Databáze: | OpenAIRE |
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