Venance L, Piomelli D, Glowinski J, Giaume C
INSERM U114, Collège de France, Paris.
Nature. 1995 Aug 17;376(6541):590-4. doi: 10.1038/376590a0.
Anandamide, an endogenous arachidonic acid derivative that is released from neurons and activates cannabinoid receptors, may act as a transcellular cannabimimetic messenger in the central nervous system. The biological actions of anandamide and the identity of its target cells are, however, still poorly documented. Here we show that anandamide is a potent inhibitor of gap-junction conductance and dye permeability in striatal astrocytes. This inhibitory effect is specific for anandamide as compared to co-released congeners or structural analogues, is sensitive to pertussis toxin and to protein-alkylating agents, and is neither mimicked by cannabinoid-receptor agonists nor prevented by a cannabinoid-receptor antagonist. Glutamate released from neurons evokes calcium waves in astrocytes that propagate via gap junctions, and may, in turn, activate neurons distant from their initiation sites in astrocytes. We find that anandamide blocks the propagation of astrocyte calcium waves generated by either mechanical stimulation or local glutamate application. Thus, by regulating gap-junction permeability, anandamide may control intercellular communication in astrocytes and therefore neuron-glial interactions.
花生四烯乙醇胺是一种从神经元释放并激活大麻素受体的内源性花生四烯酸衍生物，它可能作为中枢神经系统中的一种跨细胞类大麻信使发挥作用。然而，花生四烯乙醇胺的生物学作用及其靶细胞的身份仍鲜有文献记载。在此我们表明，花生四烯乙醇胺是纹状体星形胶质细胞中缝隙连接电导和染料通透性的强效抑制剂。与共同释放的同系物或结构类似物相比，这种抑制作用对花生四烯乙醇胺具有特异性，对百日咳毒素和蛋白质烷基化剂敏感，既不能被大麻素受体激动剂模拟，也不能被大麻素受体拮抗剂阻断。神经元释放的谷氨酸在星形胶质细胞中引发钙波，这些钙波通过缝隙连接传播，进而可能激活远离其在星形胶质细胞中起始位点的神经元。我们发现，花生四烯乙醇胺可阻断由机械刺激或局部应用谷氨酸所产生的星形胶质细胞钙波的传播。因此，通过调节缝隙连接通透性，花生四烯乙醇胺可能控制星形胶质细胞中的细胞间通讯，从而调控神经元与神经胶质细胞之间的相互作用。
