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Hyperforin - a key constituent of St. Johns wort specifically activates TRPC6 channels

Item Type:Article
Title:Hyperforin - a key constituent of St. Johns wort specifically activates TRPC6 channels
Creators Name:Leuner, K. and Kazanski, V. and Mueller, M. and Essin, K. and Henke, B. and Gollasch, M. and Harteneck, C. and Mueller, W.E.
Abstract:Hyperforin, a bicyclic polyprenylated acylphloroglucinol derivative, is the main active principle of St. Johns wort extract responsible for its antidepressive profile. Hyperforin inhibits the neuronal serotonin and norepinephrine uptake comparable to synthetic antidepressants. In contrast to synthetic antidepressants directly blocking neuronal amine uptake, hyperforin increases synaptic serotonin and norepinephrine concentrations by an indirect and yet unknown mechanism. Our attempts to identify the molecular target of hyperforin resulted in the identification of TRPC6. Hyperforin induced sodium and calcium entry as well as currents in TRPC6-expressing cells. Sodium currents and the subsequent breakdown of the membrane sodium gradients may be the rationale for the inhibition of neuronal amine uptake. The hyperforin-induced cation entry was highly specific and related to TRPC6 and was suppressed in cells expressing a dominant negative mutant of TRPC6, whereas phylogenetically related channels, i.e., TRPC3 remained unaffected. Furthermore, hyperforin induces neuronal axonal sprouting like nerve growth factor in a TRPC6-dependent manner. These findings support the role of TRPC channels in neurite extension and identify hyperforin as the first selective pharmacological tool to study TRPC6 function. Hyperforin integrates inhibition of neurotransmitter uptake and neurotrophic property by specific activation of TRPC6 and represents an interesting lead-structure for a new class of antidepressants.
Keywords:Calcium, Neurite Outgrowth, Animals, Rats
Source:FASEB Journal
Publisher:Federation of American Societies for Experimental Biology
Page Range:4101-4111
Date:December 2007
Official Publication:https://doi.org/10.1096/fj.07-8110com
PubMed:View item in PubMed

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