Hyperforin depletes synaptic vesicles content and induces compartmental redistribution of nerve ending monoamines.
Hyperforin, a phloroglucinol derivative found in Hypericum perforatum (St. John's wort) extracts has antidepressant properties in depressed patients. Hyperforin has a unique pharmacological profile and it inhibits uptake of biogenic monoamines as well as amino acid transmitters. We have recently showed that the monoamines uptake inhibition exerted by hyperforin is related to its ability to dissipate the pH gradient across the synaptic vesicle membrane thereby interfering with vesicular monoamines storage. In the present study we demonstrate that hyperforin induces dose-dependent efflux of preloaded [3H]5HT and [3H]DA from rat brain slices. Moreover, we show that hyperforin attenuates depolarization- dependent release of monoamines, while increasing monoamine release by amphetamine or fenfluramine. It is also demonstrated that preincubation of brain slices with reserpine is associated with dose- dependent blunting of efflux due to hyperforin. Our data indicate that hyperforin-induced efflux of [3H]5HT and [3H]DA reflect elevated cytoplasmic concentrations of the two monoamines secondary to the depletion of the synaptic vesicle content and the compartmental redistribution of nerve ending monoamines.
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Netta
N
Roz
Moshe
M
Rehavi
D000704:Analysis of Variance; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D001692:Biological Transport; D001921:Brain / Q000378:metabolism*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006863:Hydrogen-Ion Concentration; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000187:drug effects*; D013729:Terpenes / Q000494:pharmacology*; D013997:Time Factors; D014316:Tritium
D015306:Biogenic Monoamines; D001643:Bridged Bicyclo Compounds; D014179:Neurotransmitter Uptake Inhibitors; D013729:Terpenes; D014316:Tritium; D012701:Serotonin; D010696:Phloroglucinol; C001654:hyperforin; D004298:Dopamine