A second endogenous cannabinoid that modulates long-term potentiation
A second endogenous cannabinoid that modulates long-term potentiation
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DOI：
10.1038/42015
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发表时间：
1997-08-21
期刊：
影响因子：
64.8
通讯作者：
Piomelli, D
中科院分区：
文献类型：
--
作者：
Stella, N;Schweitzer, P;Piomelli, D
大麻素受体是大麻和印度大麻（广泛滥用的药物）的分子靶点。这些受体在中枢神经系统区域表达，对记忆、认知、运动和疼痛感知的控制发挥重要作用(1)。事实上，这些功能可能会受到大麻素药物的强烈影响，其后果包括欣快感、镇痛、镇静和记忆障碍(2)。尽管现在人们开始了解大麻素药物的药理学，但我们仍然缺乏有关大麻素受体通常参与的内源信号系统的基本信息。大麻素受体的内源性配体 anandamide 已被描述(3)。在此，我们报道了 sn-2 花生酰甘油 (2-AG) 是一种从肠道组织中分离出来的大麻素配体 (4)，其在大脑中的含量是 anandamide 的 170 倍。 2-AG 是通过刺激 Schaffer 络脉（从 CA3 神经元投射到 CA1 神经元的兴奋性纤维束）在海马切片中产生的。 2-AG 的形成是钙依赖性的，并且由磷脂酶 C 和二酰甘油脂肪酶介导。 2-AG 作为完全激动剂激活神经元大麻素受体，并阻止 CA3-CA1 突触长期增强的诱导。我们的结果表明 2-AG 是中枢神经系统中的第二种内源性大麻素配体。
Cannabinoid receptors are molecular targets for marijuana and hashish, the widespread drugs of abuse. These receptors are expressed in areas of the central nervous system that contribute in important ways to the control of memory, cognition, movement and pain perception(1). Indeed, such functions can be strongly influenced by cannabinoid drugs, with consequences that include euphoria, analgesia, sedation and memory impairment(2). Although the pharmacology of cannabinoid drugs is now beginning to be understood, we still lack essential information on the endogenous signalling system(s) by which cannabinoid receptors are normally engaged. An endogenous ligand for cannabinoid receptors, anandamide, has been described(3). Here we report that sn-2 arachidonylglycerol (2-AG), a cannabinoid ligand isolated from intestinal tissue(4), is present in brain in amounts 170 times greater than anandamide. 2-AG is produced in hippocampal slices by stimulation of the Schaffer collaterals, an excitatory fibre tract that projects from CA3 to CA1 neurons. Formation of 2-AG is calcium dependent and is mediated by the enzymes phospholipase C and diacylglycerol lipase. 2-AG activates neuronal cannabinoid receptors as a full agonist, and prevents the induction of long-term potentiation at CA3-CA1 synapses. Our results indicate that 2-AG is a second endogenous cannabinoid ligand in the central nervous system.