title: Hypericin, the active component of St. John's wort, inhibits glutamate release in the rat cerebrocortical synaptosomes via a mitogen-activated protein kinase-dependent pathway.
abstract: Changes in central glutamate neurotransmission are involved in the pathophysiology of depression and in the mechanism of antidepressants. In this study, the effect of hypericin, a major active constituent of St. John's wort that is widely used in the treatment of depression, on the release of glutamate from nerve terminals purified from rat cerebral cortex was examined. Result showed that hypericin inhibited the release of glutamate evoked by 4-aminopyridine in a concentration-dependent manner. Further experiments revealed that hypericin-mediated inhibition of glutamate release (i) results from a reduction of vesicular exocytosis, not from an inhibition of Ca2+-independent efflux via glutamate transporter; (ii) is not due to an alternation of nerve terminal excitability; (iii) is associated with a decrease in presynaptic N- and P/Q-type voltage-dependent Ca2+ channel activity; and (iv) appears to involve the suppression of mitogen-activated protein kinase pathway. These results are the first to suggest that, in rat cerebrocortical nerve terminals, hypericin suppresses voltage-dependent Ca2+ channel and mitogen-activated protein kinase activity and in so doing inhibits evoked glutamate release. This finding may provide important information regarding the beneficial effects of St. John's wort in the brain.
authors.affiliation: School of Medicine, Fu Jen Catholic University, 510 Chung-Cheng Road, Hsin-Chuang, Taipei Hsien 24205, Taiwan.
authors.forename: Yi
authors.initials: Y
authors.lastname: Chang
authors.forename: Su-Jane
authors.initials: SJ
authors.lastname: Wang
mesh_terms: D000818:Animals; D000873:Anthracenes; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000378:metabolism*; D020902:Hypericum; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010569:Perylene / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism
chemical_list: D000873:Anthracenes; D018698:Glutamic Acid; D010569:Perylene; C004965:hypericin; D020928:Mitogen-Activated Protein Kinases