An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity
An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity
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DOI：
10.1016/s0014-2999(98)00392-6
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发表时间：
1998-07-17
影响因子：
5
通讯作者：
Mechoulam, R
中科院分区：
文献类型：
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作者：
Ben-Shabat, S;Fride, E;Mechoulam, R
2-花生四烯酰基甘油（2-Ara-G1）已从多种组织中分离出来，并被鉴定为大麻素受体CB1和CB2的内源性配体。在这里，我们报道在脾脏中，就像在大脑和肠道中一样，2-Ara-G1伴随着几种2-酰基甘油酯，其中两种主要是2-亚油基甘油（2-亚麻- g1）和2-棕榈酰甘油（2-棕榈- g1）。这两种酯不与大麻素受体结合，也不通过CB1或CB2抑制腺苷酸环化酶；然而，它们显著增强了2-Ara-G1的表面结合及其抑制腺苷酸环化酶的明显能力。这些酯也显著增强了2-Ara-G1对小鼠运动行为、环上不动、热板上镇痛和低温的抑制作用。2-Lino-G1，而不是2-Palm-G1，显著抑制神经元和嗜碱性细胞对2-Ara-G1的失活。这些数据表明，相关的内源性2-酰基甘油可以增加2-Ara-G1的生物活性，而在任何所采用的测试中，单独的2-酰基甘油都没有显示出显著的活性。这种效应（“随行效应”）可能代表内源性大麻素活性分子调控的新途径。(C) 1998 Elsevier Science B.V.版权所有
2-Arachidonoyl-glycerol (2-Ara-G1) has been isolated from various tissues and identified as an endogenous ligand for both cannabinoid receptors, CB1 and CB2. Here we report that in spleen, as in brain and gut, 2-Ara-G1 is accompanied by several 2-acyl-glycerol esters, two major ones being 2-linoleoyl-glycerol (2-Lino-G1) and 2-palmitoyl-glycerol (2-Palm-G1). These two esters do not bind to the cannabinoid receptors, nor do they inhibit adenylyl cyclase via either CB1 or CB2; however, they significantly potentiate the apparent binding of 2-Ara-G1 and its apparent capacity to inhibit adenylyl cyclase. Together these esters also significantly potentiate 2-Ara-G1 inhibition of motor behavior, immobility on a ring, analgesia on a hot plate and hypothermia caused by 2-Ara-G1 in mice. 2-Lino-G1, but not 2-Palm-G1, significantly inhibits the inactivation of 2-Ara-G1 by neuronal and basophilic cells. These data indicate that the biological activity of 2-Ara-G1 can be increased by related, endogenous 2-acyl-glycerols, which alone show no significant activity in any of the tests employed. This effect ('entourage effect') may represent a novel route for molecular regulation of endogenous cannabinoid activity. (C) 1998 Elsevier Science B.V. All rights reserved.