2-arachidonoyl-sn-glycero-3-phosphate, an arachidonic acid-containing lysophosphatidic acid:: occurrence and rapid enzymatic conversion to 2-arachidonoyl-sn-glycerol, a cannabinoid receptor ligand, in rat brain
2-arachidonoyl-sn-glycero-3-phosphate, an arachidonic acid-containing lysophosphatidic acid:: occurrence and rapid enzymatic conversion to 2-arachidonoyl-sn-glycerol, a cannabinoid receptor ligand, in rat brain
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DOI：
10.1016/s0003-9861(02)00038-3
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发表时间：
2002-06-01
影响因子：
3.9
通讯作者：
Sugiura, T
中科院分区：
文献类型：
--
作者：
Nakane, S;Oka, S;Sugiura, T
在液氮致死大鼠的脑组织中发现了大量溶血磷脂酸（LPA） （15.66 nmol/g组织）。我们发现含有花生四烯酸的种类占脑LPA的很大一部分（5.4%）。结果表明，LPA存在2-花生四烯酰基和1-花生四烯酰基两种。脑中2-花生四烯醇LPA （0.53 nmol/g组织）的出现是一个值得注意的观察，因为它的结构与内源性大麻素受体配体2-花生四烯醇sn-甘油（2-AG）相似。然后，我们使用同时表达LPA受体和大麻素CB1受体的神经母细胞瘤x胶质瘤杂交细胞NG108-15，检测了2-花生四烯醇LPA的生物活性，并将其与2-AG的生物活性进行了比较。我们发现2-花生四烯醇LPA与LPA受体相互作用，引起细胞内游离Ca2+浓度的升高，而2-AG只与大麻素CB1受体相互作用。接下来，我们研究了2-花生四烯醇LPA和2-AG之间可能的代谢关系，并获得了明确的证据，表明2-花生四烯醇LPA在脑浆液中快速酶转化为2-AG。值得注意的是，两种内源性配体与不同类型的受体相互作用，在代谢上密切相关，并迅速相互转化。(C) 2002 Elsevier Science （USA）。版权所有。
A substantial amount of lysophosphatidic acid (LPA) (15.66 nmol/g tissue) was found to occur in the brain isolated from rats killed in liquid nitrogen. We found that a significant portion of brain LPA was accounted for by the arachidonic acid-containing species (5.4%). We obtained evidence that both 2-arachidonoyl species and 1-arachidonoyl species of LPA are present. The occurrence of 2-arachidonoyl LPA in the brain (0.53 nmol/g tissue) is a notable observation, because of its structural resemblance to 2-arachidonoyl-sn-glycerol (2-AG), an endogenous cannabinoid receptor ligand. We then examined the biological activity of 2-arachidonoyl LPA and compared it with that of 2-AG using neuroblastoma x glioma hybrid NG108-15 cells which express both the LPA receptor and cannabinoid CB1 receptor. We found that 2-arachidonoyl LPA interacts with the LPA receptor(s) to elicit the elevation of intracellular free Ca2+, concentrations, whereas 2-AG interacts exclusively with the cannabinoid CB1 receptor. Next, we examined the possible metabolic relationship between 2-arachidonoyl LPA and 2-AG and obtained clear evidence that rapid enzymatic conversion of 2-arachidonoyl LPA to 2-AG took place in the brain homogenate. It is noteworthy that two types of endogenous ligands, that interact with different types of receptors, are closely related metabolically and rapidly interconvert. (C) 2002 Elsevier Science (USA). All rights reserved.