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Hyperforin depletes synaptic vesicles content and induces compartmental redistribution of nerve ending monoamines

机译：Hyperforin耗尽突触小泡的含量，并诱导神经末梢单胺的区室再分布

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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 [H-3]5HT and [H-3]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 [H-3]5HT and [H-3]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. (C) 2004 Elsevier Inc. All rights reserved.
机译：Hyperforin，一种在贯叶连翘（圣约翰草）提取物中发现的间苯三酚衍生物，对抑郁症患者具有抗抑郁作用。 Hyperforin具有独特的药理作用，可抑制生物单胺以及氨基酸递质的摄取。最近我们已经表明，由hyperforin产生的单胺摄取抑制作用与其消散整个突触小泡膜的pH梯度从而干扰小泡单胺储存有关。在本研究中，我们证明了超forin可以诱导大鼠脑切片中预载的[H-3] 5HT和[H-3] DA的剂量依赖性流出。此外，我们表明，hyperforin会减弱单胺的去极化依赖性释放，同时会增加苯丙胺或芬氟拉明的单胺释放。还证明了脑片与利血平的预温育与由于hyperforin引起的剂量依赖性外排钝化有关。我们的数据表明高forin诱导的[H-3] 5HT和[H-3] DA的流出反映了继突触小泡含量的耗尽和神经末梢单胺的区室再分布后，两种单胺的细胞质浓度升高。 （C）2004 Elsevier Inc.保留所有权利。

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