Endocannabinoids and Their Pharmacological Actions
Endocannabinoids and Their Pharmacological Actions
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DOI：
10.1007/978-3-319-20825-1_1
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发表时间：
2015-01-01
期刊：
影响因子：
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通讯作者：
Pertwee, Roger G.
中科院分区：
文献类型：
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作者：
Pertwee, Roger G.
内源性大麻素系统由 G 蛋白偶联的大麻素 CB1 和 CB2 受体、可靶向这些受体的称为内源性大麻素的内源性化合物、催化内源性大麻素生物合成和代谢的酶以及负责细胞摄取某些内源性大麻素的过程组成。本综述提出了体外证据，表明以下 13 种化合物中的大多数或全部可能是正位内源性大麻素，因为它们都在一项或多项研究中在哺乳动物组织中检测到，并且全部被发现与大麻素受体结合，可能与正位位点结合：anandamide、2-花生四烯酰甘油、noladin 醚、二高-.-亚麻酰乙醇酰胺、virodhamine、油酰胺、二十二碳六烯酰乙醇酰胺、二十碳五烯酰乙醇酰胺、鞘氨醇、二十二碳四烯酰乙醇酰胺、N-花生四烯酰多巴胺、N-油酰多巴胺和血加压素。此外，这篇综述描述了体外研究结果，表明这些化合物中的前八种可以激活 CB1，有时也可以激活 CB2 受体，另外两种化合物是 CB1 受体拮抗剂（鞘氨醇）或拮抗剂/反向激动剂（血加压素）。还提供了至少三种变构内源性大麻素存在的证据。这些内源性化合物似乎在体外靶向大麻素受体上的变构位点，作为 CB1 受体（pepcan-12 和孕烯醇酮）的负变构调节剂，或作为该受体（脂氧素 A4）或 CB2 受体（pepcan-12）的正变构调节剂。还讨论了当前的体外数据，这些数据表明一些已确定或推定的正位内源性大麻素似乎靶向非大麻素受体和离子通道的程度，特别是在发现它们与 CB1 或 CB2 受体相互作用的浓度下。
The endocannabinoid system consists of G protein-coupled cannabinoid CB1 and CB2 receptors, of endogenous compounds known as endocannabinoids that can target these receptors, of enzymes that catalyse endocannabinoid biosynthesis and metabolism, and of processes responsible for the cellular uptake of some endocannabinoids. This review presents in vitro evidence that most or all of the following 13 compounds are probably orthosteric endocannabinoids since they have all been detected in mammalian tissues in one or more investigation, and all been found to bind to cannabinoid receptors, probably to an orthosteric site: anandamide, 2-arachidonoylglycerol, noladin ether, dihomo-.-linolenoylethanolamide, virodhamine, oleamide, docosahexaenoylethanolamide, eicosapentaenoylethanolamide, sphingosine, docosatetraenoylethanolamide, N-arachidonoyldopamine, N-oleoyldopamine and haemopressin. In addition, this review describes in vitro findings that suggest that the first eight of these compounds can activate CB1 and sometimes also CB2 receptors and that another two of these compounds are CB1 receptor antagonists (sphingosine) or antagonists/inverse agonists (haemopressin). Evidence for the existence of at least three allosteric endocannabinoids is also presented. These endogenous compounds appear to target allosteric sites on cannabinoid receptors in vitro, either as negative allosteric modulators of the CB1 receptor (pepcan-12 and pregnenolone) or as positive allosteric modulators of this receptor (lipoxin A4) or of the CB2 receptor (pepcan-12). Also discussed are current in vitro data that indicate the extent to which some established or putative orthosteric endocannabinoids seem to target non-cannabinoid receptors and ion channels, particularly at concentrations at which they have been found to interact with CB1 or CB2 receptors.