title: Curcumin inhibits glutamate release in nerve terminals from rat prefrontal cortex: possible relevance to its antidepressant mechanism.
abstract: There is abundant evidence suggesting the relevance of glutamate to depression and antidepressant mechanisms. Curcumin, a major active compound of Curcuma longa, has been reported to have the biological function of antidepressant. The aim of the present study was to investigate the effect of curcumin on endogenous glutamate release in nerve terminals of rat prefrontal cortex and the underlying mechanisms. The results showed that curcumin inhibited the release of glutamate that was evoked by exposing synaptosomes to the K(+) channel blocker 4-aminopyridine (4-AP). This phenomenon was blocked by the chelating the extracellular Ca(2+) ions, and by the vesicular transporter inhibitor bafilomycin A1, but was insensitive to the glutamate transporter inhibitor DL-threo-β-benzyl-oxyaspartate (DL-TBOA). Further experiments demonstrated that curcumin decreased depolarization-induced increase in [Ca(2+)](C), whereas it did not alter the resting membrane potential or 4-AP-mediated depolarization. Furthermore, the inhibitory effect of curcumin on evoked glutamate release was prevented by blocking the Ca(v)2.2 (N-type) and Ca(v)2.1 (P/Q-type) channels, but not by blocking intracellular Ca(2+) release or Na(+)/Ca(2+) exchange. These results suggest that curcumin inhibits evoked glutamate release from rat prefrontocortical synaptosomes by the suppression of presynaptic Ca(v)2.2 and Ca(v)2.1 channels. Additionally, we also found that the inhibitory effect of curcumin on 4-AP-evoked glutamate release was completely abolished by the clinically effective antidepressant fluoxetine. This suggests that curcumin and fluoxetine use a common intracellular mechanism to inhibit glutamate release from rat prefrontal cortex nerve terminals.
authors: Department of Anesthesiology, Far-Eastern Memorial Hospital, New Taipei City, 220 Taiwan.
authors: Tzu Yu
authors: TY
authors: Lin
authors: Cheng Wei
authors: CW
authors: Lu
authors: Chia-Chuan
authors: CC
authors: Wang
authors: Ying-Chou
authors: YC
authors: Wang
authors: Su-Jane
authors: SJ
authors: Wang
mesh_terms: D015761:4-Aminopyridine / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002118:Calcium / Q000032:analysis / Q000502:physiology; D003474:Curcumin / Q000494:pharmacology*; D018698:Glutamic Acid / Q000032:analysis / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009411:Nerve Endings / Q000187:drug effects / Q000502:physiology; D026902:Potassium Channel Blockers / Q000378:metabolism / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000187:drug effects / Q000502:physiology
chemical_list: D000928:Antidepressive Agents; D026902:Potassium Channel Blockers; D018698:Glutamic Acid; D015761:4-Aminopyridine; D003474:Curcumin; D002118:Calcium