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Incensole acetate an incense component elicits psychoactivity by activating TRPV3 channels in the brain

机译:醋酸香豆酚是一种熏香成分可通过激活大脑中的TRPV3通道引发精神活性

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摘要

Burning of Boswellia resin as incense has been part of religious and cultural ceremonies for millennia and is believed to contribute to the spiritual exaltation associated with such events. Transient receptor potential vanilloid (TRPV) 3 is an ion channel implicated in the perception of warmth in the skin. TRPV3 mRNA has also been found in neurons throughout the brain; however, the role of TRPV3 channels there remains unknown. Here we show that incensole acetate (IA), a Boswellia resin constituent, is a potent TRPV3 agonist that causes anxiolytic-like and antidepressive-like behavioral effects in wild-type (WT) mice with concomitant changes in c-Fos activation in the brain. These behavioral effects were not noted in TRPV3−/− mice, suggesting that they are mediated via TRPV3 channels. IA activated TRPV3 channels stably expressed in HEK293 cells and in keratinocytes from TRPV3+/+ mice. It had no effect on keratinocytes from TRPV3−/− mice and showed modest or no effect on TRPV1, TRPV2, and TRPV4, as well as on 24 other receptors, ion channels, and transport proteins. Our results imply that TRPV3 channels in the brain may play a role in emotional regulation. Furthermore, the biochemical and pharmacological effects of IA may provide a biological basis for deeply rooted cultural and religious traditions.—Moussaieff, A., Rimmerman, N., Bregman, T., Straiker, A., Felder, C. C., Shoham, S., Kashman, Y., Huang, S. M., Lee, H., Shohami, E., Mackie, K., Caterina, M. J., Walker, J. M., Fride, E., Mechoulam, R. Incensole acetate, an incense component, elicits psychoactivity by activating TRPV3 channels in the brain.
机译:几千年来,作为香火燃烧乳香树脂已成为宗教和文化仪式的一部分,并被认为有助于与此类事件相关的精神上的提升。瞬态受体电位香草酸(TRPV)3是一个与皮肤温暖感相关的离子通道。在整个大脑的神经元中也发现了TRPV3 mRNA。但是,TRPV3通道的作用仍然未知。在这里,我们显示了乳香木犀草酸酯树脂(IA),一种乳香树脂成分,是一种有效的TRPV3激动剂,可在野生型(WT)小鼠中引起抗焦虑样和抗抑郁样的行为效应,并伴随大脑中c-Fos激活的变化。在TRPV3 -/-小鼠中未注意到这些行为效应,表明它们是通过TRPV3通道介导的。 IA激活了TRPV3 + / + 小鼠的HEK293细胞和角质形成细胞中稳定表达的TRPV3通道。它对TRPV3 -/-小鼠的角质形成细胞没有影响,对TRPV1,TRPV2和TRPV4以及其他24种受体,离子通道和转运蛋白也没有影响。我们的结果表明,大脑中的TRPV3通道可能在情绪调节中起作用。此外,IA的生化和药理作用可能为根深蒂固的文化和宗教传统提供生物学基础。—Moussaieff,A.,Rimmerman,N.,Bregman,T.,Straiker,A.,Felder,CC,Shoham,S 。,Kashman,Y.,Huang,SM,Lee,H.,Shohami,E.,Mackie,K.,Caterina,MJ,Walker,JM,Fride,E.,Mechoulam,R.通过激活大脑中的TRPV3通道引发精神活动。

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