二酰基甘油脂肪酶（DAGL）在尼古丁戒断中的差异作用。
Differential roles of diacylglycerol lipase (DAGL) enzymes in nicotine withdrawal.
机构信息
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA.
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA; Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA, USA.
出版信息
Brain Res. 2023 Oct 15;1817:148483. doi: 10.1016/j.brainres.2023.148483. Epub 2023 Jul 11.
Nicotine and tobacco-related deaths remains a leading cause of preventable death and disease in the United States. Several studies indicate that modulation of the endocannabinoid system, primarily of the endocannabinoid 2-Arachidonoylglycerol (2-AG), alters nicotinic dependence behaviors in rodents. This study, using transgenic knock-out (KO) mice, evaluated the role of the two 2-AG biosynthesis enzymes, (Diacylglycerol lipase-α) DAGL-α and DAGL-β in spontaneous nicotine withdrawal. DAGL-α deletion prevents somatic and affective signs of nicotine withdrawal, while DAGL-β deletion plays a role in hyperalgesia due to nicotine withdrawal. These results suggest a differential role of these enzymes in the various signs of nicotine withdrawal. Our behavioral findings relate to the distribution of these enzymes with DAGL-β being highly expressed in macrophages and DAGL-α in neurons. This study offers new potential targets for smoking cessation therapies.
尼古丁和与烟草相关的死亡仍然是美国可预防死亡和疾病的主要原因。几项研究表明，内源性大麻素系统的调节，主要是内源性大麻素 2-花生四烯酸甘油（2-AG），改变了啮齿动物的尼古丁依赖行为。本研究使用转基因敲除（KO）小鼠，评估了两种 2-AG 生物合成酶（二酰基甘油脂肪酶-α）DAGL-α 和 DAGL-β 在自发性尼古丁戒断中的作用。DAGL-α 缺失可预防尼古丁戒断的躯体和情感症状，而 DAGL-β 缺失在尼古丁戒断引起的痛觉过敏中发挥作用。这些结果表明这些酶在尼古丁戒断的各种症状中具有不同的作用。我们的行为学发现与这些酶的分布有关，DAGL-β 在巨噬细胞中高度表达，DAGL-α 在神经元中表达。这项研究为戒烟治疗提供了新的潜在靶点。
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