Department of Psychological and Brain Sciences at Indiana University, Bloomington, IN 47405, USA.
Life Sci. 2013 Mar 19;92(8-9):404-9. doi: 10.1016/j.lfs.2012.11.008. Epub 2012 Nov 20.
Transient receptor potential channels (TRPs) form a large family of ubiquitous non-selective cation channels that function as cellular sensors and in many cases regulate intracellular calcium. Identification of the endogenous ligands that activate these TRP receptors is still under intense investigation with the majority of these channels still remaining "orphans." That these channels respond to a variety of external stimuli (e.g. plant-derived lipids, changes in temperature, and changes in pH) provides a framework for their abilities as cellular sensors, however, the mechanism of direct activation is still under much debate and research. In the cases where endogenous ligands (predominately lipids) have shown direct activation of a channel, multiple ligands have been shown to activate the same channel suggesting that these receptors are "promiscuous" in nature. Lipidomics of a growing class of endogenous lipids, N-acyl amides, the most famous of which is N-arachidonoyl ethanolamine (the endogenous cannabinoid, Anandamide) is providing a novel set of ligands that have been shown to activate some members of the TRP family and have the potential to deorphanize many more. Here it is argued that activation of TRPV receptors, a subset of the larger family of TRPs, by multiple endogenous lipids that are structurally analogous is a model system to drive our understanding that many TRP receptors are not promiscuous, but are more characteristically "opportunistic" in nature; exploiting the structural similarity and biosynthesis of a narrow range of analogous endogenous lipids. In addition, this manuscript will compare the activation properties of TRPC5 to the activity profile of an "orphan" lipid, N-palmitoyl glycine; further demonstrating that lipidomics aimed at expanding our knowledge of the family of N-acyl amides has the potential to provide novel avenues of research for TRP receptors.
瞬时受体电位通道（TRP）形成一个广泛存在的非选择性阳离子通道家族，作为细胞传感器发挥作用，在许多情况下调节细胞内钙。鉴定激活这些 TRP 受体的内源性配体仍在深入研究中，其中大多数通道仍然是“孤儿”。这些通道对各种外部刺激（例如植物衍生的脂质、温度变化和 pH 值变化）作出反应，为它们作为细胞传感器的能力提供了一个框架，然而，直接激活的机制仍存在很大争议和研究。在已经显示内源性配体（主要是脂质）直接激活通道的情况下，已经表明多种配体可以激活相同的通道，这表明这些受体在性质上是“混杂的”。越来越多的内源性脂质，N-酰基酰胺的脂质组学，其中最著名的是 N-花生四烯酰乙醇胺（内源性大麻素，花生四烯酰胺），提供了一组新的配体，这些配体已被证明可以激活 TRP 家族的一些成员，并有可能使更多的成员“非孤儿化”。这里认为，多种结构类似的内源性脂质激活 TRPV 受体（TRP 大家族的一个子集）是一个模型系统，可以推动我们理解许多 TRP 受体不是混杂的，而是更具“机会主义”的性质；利用结构相似性和窄范围类似内源性脂质的生物合成。此外，本文将比较 TRPC5 的激活特性与“孤儿”脂质 N-棕榈酰甘氨酸的活性特征；进一步表明，旨在扩大我们对 N-酰基酰胺家族的了解的脂质组学有可能为 TRP 受体提供新的研究途径。
