Activation of TRPC6 channels promotes endocannabinoid biosynthesis in neuronal CAD cells.
Activation of TRPC6 channels promotes endocannabinoid biosynthesis in neuronal CAD cells.
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DOI：
10.1016/j.neuint.2010.05.002
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发表时间：
2010-08
影响因子：
4.2
通讯作者：
Barker, Eric L.
中科院分区：
文献类型：
--
作者：
Bardell, Tamera K.;Barker, Eric L.
钙内流激活内源性大麻素2-花生四烯酰基甘油（2-AG）和大麻酰胺（AEA）的生物合成。神经元中与内源性大麻素合成和释放有关的钙通道尚不清楚。典型TRP （TRPC）通道是钙渗透通道，是更广泛的TRP通道的同源性分支。TRPC3、6和7是g蛋白门控的非选择性阳离子通道，已经定位于脂筏，并显示与小泡蛋白1共定位。由于内源性大麻素的合成已被发现以钙依赖的方式“按需”发生，并与脂筏有关，我们探索了瞬时受体电位（TRP）通道在这一过程中的潜在作用。在此之前，我们观察到AEA和花生四烯酸（ArA）经过代谢后可以再循环成新的内源性大麻素分子。与这些先前的发现一致，我们发现Cath。用放射标记ArA预处理的分化（CAD）细胞在二酰基甘油（DAG）类似物1-油基-2-乙酰基-sn-甘油（OAG）刺激TRPC后，2-AG的释放明显增加。此外，用[3H]AEA预处理的细胞在刺激TRPC通道后产生大量的AEA和2-AG。这个过程不是通过蛋白激酶C激活介导的。逆转录聚合酶链反应（RT-PCR）分析显示，只有TRPC6存在于CAD细胞中。sirna诱导的CAD细胞中TRPC6的敲低消除了oag刺激的内源性大麻素的产生。这一证据表明TRPC6可能能够促进神经细胞内源性大麻素的合成。
Calcium influx activates biosynthesis of the endogenous cannabinoids 2-arachidonyl glycerol (2-AG) and anandamide (AEA). The calcium channel involved with endocannabinoid synthesis and release in neurons is still unknown. The canonical TRP (TRPC) channels are calcium-permeable channels that are a homology-based subdivision of the broader class of TRP channels. TRPC3, 6, and 7 are G-protein-gated nonselective cation channels that have been localized to lipid rafts and shown to colocalize with caveolin 1. Because endocannabinoid synthesis has been found to occur “on demand” in a calcium-dependent manner and has been linked to lipid rafts, we explored the potential role of transient receptor potential (TRP) channels in this process. Previously, we observed that after metabolism AEA and arachidonic acid (ArA) can be recycled into new endocannabinoid molecules. Consistent with these previous findings, we found that Cath.a differentiated (CAD) cells pretreated with radiolabeled ArA exhibited a robust increase in 2-AG release in response to TRPC stimulation with the diacylglycerol (DAG) analogue, 1-oleoyl-2-acetyl-sn-glycerol (OAG). Furthermore, cells pretreated with [3H]AEA produced a significant amount of AEA and 2-AG upon stimulation of TRPC channels. This process was not mediated through protein kinase C activation. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed that only TRPC6 was present in the CAD cells. siRNA-induced knockdown of TRPC6 in the CAD cells abolished OAG-stimulated production of the endocannabionids. This evidence suggests that TRPC6 may be capable of promoting endocannabinoid synthesis in neuronal cells.
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影响因子：
3.6
作者：
Carrier, EJ;Kearn, CS;Hillard, CJ
通讯作者：
Hillard, CJ
影响因子：
4.8
作者：
Lockwich, T;Singh, BB;Ambudkar, IS
通讯作者：
Ambudkar, IS
影响因子：
4.1
作者：
Bisogno, T;Sepe, N;DiMarzo, V
通讯作者：
DiMarzo, V
影响因子：
3.6
作者：
Bisogno, T;Ligresti, A;Di Marzo, V
通讯作者：
Di Marzo, V
影响因子：
4.8
作者：
Lemonnier, L;Trebak, M;Putney, JW
通讯作者：
Putney, JW