URB754对大鼠大脑中2-花生四烯酸甘油（2-AG）的水解或信号传导能力没有影响。
URB754 has no effect on the hydrolysis or signaling capacity of 2-AG in the rat brain.
作者信息
Saario Susanna M, Palomäki Ville, Lehtonen Marko, Nevalainen Tapio, Järvinen Tomi, Laitinen Jarmo T
机构信息
Department of Pharmaceutical Chemistry, Department of Physiology, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland.
出版信息
Chem Biol. 2006 Aug;13(8):811-4. doi: 10.1016/j.chembiol.2006.07.008.
Previous studies indicate that in brain tissue the endocannabinoid 2-AG is inactivated by monoglyceride lipase (MGL)-catalyzed hydrolysis, and a recent report has indicated that MGL activity could be specifically inhibited by URB754 . In the present study, URB754 failed to inhibit 2-AG hydrolysis in rat brain preparations. In addition, brain cryosections were employed to assess whether URB754 could facilitate the detection of 2-AG-stimulated G protein activity. Nevertheless, whereas pretreatment with PMSF readily allowed detection of 2-AG-stimulated G protein activity, URB754 was ineffective. In contrast to previous claims, brain FAAH activity was also resistant to URB754. Thus, in our hands URB754 was not able to block the endocannabinoid-hydrolyzing enzymes and cannot serve as a lead structure for future development of MGL-specific inhibitors.
先前的研究表明，在脑组织中，内源性大麻素2-花生四烯酸甘油酯（2-AG）通过甘油单酯脂肪酶（MGL）催化的水解作用失活，并且最近的一份报告指出，URB754可以特异性抑制MGL的活性。在本研究中，URB754未能抑制大鼠脑制备物中2-AG的水解。此外，采用脑冰冻切片来评估URB754是否能够促进对2-AG刺激的G蛋白活性的检测。然而，尽管用苯甲基磺酰氟（PMSF）预处理能够轻易检测到2-AG刺激的G蛋白活性，但URB754却没有效果。与先前的说法相反，脑脂肪酸酰胺水解酶（FAAH）的活性也对URB754具有抗性。因此，在我们的实验中，URB754无法阻断内源性大麻素水解酶，不能作为未来开发MGL特异性抑制剂的先导结构。
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