Di Marzo V, Fontana A, Cadas H, Schinelli S, Cimino G, Schwartz J C, Piomelli D
Unité de Neurobiologie et Pharmacologie, Centre Paul Broca de l'INSERM, Paris, France.
Nature. 1994 Dec 15;372(6507):686-91. doi: 10.1038/372686a0.
Anandamide (N-arachidonoyl-ethanolamine) was recently identified as a brain arachidonate derivative that binds to and activates cannabinoid receptors, yet the mechanisms underlying formation, release and inactivation of this putative messenger molecule are still unclear. Here we report that anandamide is produced in and released from cultured brain neurons in a calcium ion-dependent manner when the neurons are stimulated with membrane-depolarizing agents. Anandamide formation occurs through phosphodiesterase-mediated cleavage of a novel phospholipid precursor, N-arachidonoyl-phosphatidylethanolamine. A similar mechanism also governs the formation of a family of anandamide congeners, whose possible roles in neuronal signalling remain unknown. Our results and those of others indicate therefore that multiple biochemical pathways may participate in anandamide formation in brain tissue. The life span of extracellular anandamide is limited by a rapid and selective process of cellular uptake, which is accompanied by hydrolytic degradation to ethanolamine and arachidonate. Our results thus strongly support the proposed role of anandamide as an endogenous neuronal messenger.
花生四烯酸乙醇胺（N-花生四烯酰基乙醇胺）最近被鉴定为一种脑花生四烯酸衍生物，它能与大麻素受体结合并激活该受体，然而这种假定的信使分子的形成、释放和失活的潜在机制仍不清楚。在此我们报告，当用膜去极化剂刺激培养的脑神经元时，花生四烯酸乙醇胺以钙离子依赖的方式在神经元中产生并释放。花生四烯酸乙醇胺的形成是通过磷酸二酯酶介导的一种新型磷脂前体N-花生四烯酰基磷脂酰乙醇胺的裂解。类似的机制也控制着一类花生四烯酸乙醇胺同系物的形成，它们在神经元信号传导中的可能作用仍然未知。因此，我们的结果和其他人的结果表明，多种生化途径可能参与脑组织中花生四烯酸乙醇胺的形成。细胞外花生四烯酸乙醇胺的寿命受细胞快速选择性摄取过程的限制，这一过程伴随着水解降解为乙醇胺和花生四烯酸。因此，我们的结果有力地支持了花生四烯酸乙醇胺作为内源性神经元信使的假定作用。
