INSERM, Neurocentre Magendie, Physiopathologie de plasticité neuronale, Endocannabinoids and Neuroadaptation, U862, Bordeaux, France.
Nat Neurosci. 2012 Mar 4;15(4):558-64. doi: 10.1038/nn.3053.
The mammalian brain is one of the organs with the highest energy demands, and mitochondria are key determinants of its functions. Here we show that the type-1 cannabinoid receptor (CB(1)) is present at the membranes of mouse neuronal mitochondria (mtCB(1)), where it directly controls cellular respiration and energy production. Through activation of mtCB(1) receptors, exogenous cannabinoids and in situ endocannabinoids decreased cyclic AMP concentration, protein kinase A activity, complex I enzymatic activity and respiration in neuronal mitochondria. In addition, intracellular CB(1) receptors and mitochondrial mechanisms contributed to endocannabinoid-dependent depolarization-induced suppression of inhibition in the hippocampus. Thus, mtCB(1) receptors directly modulate neuronal energy metabolism, revealing a new mechanism of action of G protein-coupled receptor signaling in the brain.
哺乳动物的大脑是能量需求最高的器官之一，而线粒体是其功能的关键决定因素。在这里，我们发现 1 型大麻素受体 (CB(1)) 存在于小鼠神经元线粒体 (mtCB(1)) 的膜上，在那里它直接控制细胞呼吸和能量产生。通过激活 mtCB(1) 受体，外源性大麻素和原位内源性大麻素降低了细胞内环腺苷酸浓度、蛋白激酶 A 活性、复合物 I 酶活性和神经元线粒体的呼吸作用。此外，细胞内 CB(1) 受体和线粒体机制有助于内源性大麻素依赖的去极化诱导的海马抑制的抑制作用。因此，mtCB(1) 受体直接调节神经元能量代谢，揭示了 G 蛋白偶联受体信号在大脑中的新作用机制。
