Valenti M, Viganò D, Casico M G, Rubino T, Steardo L, Parolaro D, Di Marzo V
Endocannabinoid Research Group, Istituto di Chimica Biomolecolare, Via Campi Flegrei 34, Comprensorio Olivetti, Fabbricato 70, 80078 Pozzuoli, Italy.
Cell Mol Life Sci. 2004 Apr;61(7-8):945-50. doi: 10.1007/s00018-003-3453-5.
The endogenous ligands of cannabinoid receptors, also known as endocannabinoids, have been implicated in many physiological and pathological processes of the central nervous system. Here we show that the levels of the two major endocannabinoids, anandamide and 2-arachidonoyl-glycerol (2-AG), in four areas of the rat brain, change dramatically between the light and dark phases of the day. While anandamide levels in the nucleus accumbens, pre-frontal cortex, striatum and hippocampus were significantly higher in the dark phase, the opposite was observed with 2-AG, whose levels were significantly higher during the light phase in all four regions. We found that the activity of the fatty acid amide hydrolase, which catalyzes the metabolism of anandamide, was significantly lower during the dark phase, thus providing a possible explaination for the increase in anandamide levels. However, the activities of monoacylglycerol lipase and diacylglycerol lipase, two of the possible enzymes catalyzing the degradation and biosynthesis of 2-AG, respectively, changed significantly only in the striatum. These data suggest that the levels of the two major endocannabinoids might be under the control of endogenous factors known to undergo diurnal variations, and underscore the different roles, suggested by previous studies, of anandamide and 2-AG in neurophysiological processes.
大麻素受体的内源性配体，也被称为内源性大麻素，已被证明参与中枢神经系统的许多生理和病理过程。在此我们表明，大鼠大脑四个区域中两种主要内源性大麻素，花生四烯乙醇胺和2-花生四烯酸甘油酯（2-AG）的水平，在白天的明相和暗相之间会发生显著变化。伏隔核、前额叶皮质、纹状体和海马体中的花生四烯乙醇胺水平在暗相中显著更高，而2-AG则相反，其水平在所有四个区域的明相中显著更高。我们发现，催化花生四烯乙醇胺代谢的脂肪酸酰胺水解酶的活性在暗相中显著降低，从而为花生四烯乙醇胺水平的升高提供了一种可能的解释。然而，单酰甘油脂肪酶和二酰甘油脂肪酶的活性，这两种分别可能催化2-AG降解和生物合成的酶，仅在纹状体中发生了显著变化。这些数据表明，两种主要内源性大麻素的水平可能受已知经历昼夜变化的内源性因素控制，并强调了先前研究表明的花生四烯乙醇胺和2-AG在神经生理过程中的不同作用。
