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内源性大麻素系统存在于视网膜的Rod Outer Segments 中,并受光调节。

The Endocannabinoid System Is Present in Rod Outer Segments from Retina and Is Modulated by Light.

机构信息

Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB, UNS-CONICET), Edificio E1, Camino La Carrindanga km 7, 8000, Bahía Blanca, Argentina.

Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, San Juan 670, 8000, Bahía Blanca, Argentina.

出版信息

Mol Neurobiol. 2019 Nov;56(11):7284-7295. doi: 10.1007/s12035-019-1603-5. Epub 2019 Apr 24.

Abstract

The aim of the present research was to evaluate if the endocannabinoid system (enzymes and receptors) could be modulated by light in rod outer segment (ROS) from bovine retina. First, we analyzed endocannabinoid 2-arachidonoylglycerol (2-AG) metabolism in purified ROS obtained from dark-adapted (DROS) or light-adapted (LROS) retinas. To this end, diacylglycerol lipase (DAGL), monoacylglycerol lipase (MAGL), and lysophosphatidate phosphohydrolase (LPAP) enzymatic activities were analyzed using radioactive substrates. The protein content of these enzymes and of the receptors to which cannabinoids bind was determined by immunoblotting under light stimulus. Our results indicate that whereas DAGL and MAGL activities were stimulated in retinas exposed to light, no changes were observed in LPAP activity. Interestingly, the protein content of the main enzymes involved in 2-AG metabolism, phospholipase C β (PLCβ), and DAGLα (synthesis), and MAGL (hydrolysis), was also modified by light. PLCβ content was increased, while that of lipases was decreased. On the other hand, light produced an increase in the cannabinoid receptors CB1 and CB2 and a decrease in GPR55 protein levels. Taken together, our results indicate that the endocannabinoid system (enzymes and receptors) depends on the illumination state of the retina, suggesting that proteins related to phototransduction phenomena could be involved in the effects observed.

摘要

本研究旨在评估内源性大麻素系统(酶和受体)是否可以通过光在牛视网膜的光感受器外段(ROS)中进行调节。首先,我们分析了来自暗适应(DROS)或光适应(LROS)视网膜的纯化 ROS 中的内源性大麻素 2-花生四烯酸甘油(2-AG)代谢。为此,使用放射性底物分析了二酰基甘油脂肪酶(DAGL)、单酰基甘油脂肪酶(MAGL)和溶血磷脂酸磷酸水解酶(LPAP)的酶活性。在光刺激下,通过免疫印迹法测定这些酶和与大麻素结合的受体的蛋白含量。我们的结果表明,尽管暴露于光下的视网膜中 DAGL 和 MAGL 活性受到刺激,但 LPAP 活性没有变化。有趣的是,2-AG 代谢的主要酶,即磷脂酶 Cβ(PLCβ)、DAGLα(合成)和 MAGL(水解)的蛋白含量也被光改变。PLCβ 含量增加,而脂肪酶含量减少。另一方面,光导致大麻素受体 CB1 和 CB2 增加,GPR55 蛋白水平降低。总之,我们的结果表明内源性大麻素系统(酶和受体)取决于视网膜的照明状态,这表明与光转导现象相关的蛋白质可能参与了观察到的效应。

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