Effects of cannabinoids on the activities of mouse brain lipases.
Effects of cannabinoids on the activities of mouse brain lipases.
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大麻素对小鼠脑脂肪酶活性的影响。
DOI：
10.1007/bf00966122
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发表时间：
1986
影响因子：
4.4
通讯作者：
Renzulli,L
中科院分区：
文献类型：
--
作者：
Hunter,SA;Burstein,S;Renzulli,L
研究发现，大麻素可增强小鼠脑内突触体、髓鞘和线粒体的磷脂酶活性并改善其脂质水平。三角洲-1-四氢大麻酚(Δ-1-THc)及其代谢产物可剂量依赖性(0.32-16μM)刺激磷脂酶A2(PLA2)活性，使外源性[1-14C]磷脂酰胆碱(PC)释放的花生四烯酸增加。大麻素类化合物对PLA2活性的调节作用约为：7-OH-Δ1-THc&Gt；Δ1-Thc&Gt；7-oxo-Δ1-Thc&Gt；Δ1-Thc-70酸=6αOH-Δ1-Thc≫6β-OH-Δ1-Thc。Δ1-THc可显著促进突触体磷脂酶C对磷脂酰肌醇(PI)的降解，并使二酰甘油水平提高100%以上。相反，花生四烯酸是2万粒磷脂酶活性的主要产物。Δ1-THc抑制突触体甘油二酯脂肪酶活性。[1-14C]花生四烯酸很容易被结合到亚细胞膜磷脂中，并在暴露于大麻素后导致磷酸甘油三酯水平降低，随之而来的是释放的中性脂质产物增加。这些数据表明，大麻素通过激活磷脂酶来控制小鼠脑内磷脂的周转和代谢，并可能通过这一机制发挥其部分作用。
Cannabinoids were found to augment phospholipase activities and modify lipid levels of mouse brain synaptosomes, myelin and mitochondria. Delta-1-tetrahydrocannabinol (Δ1-THC) and several of its metabolites induced a dose-dependent (0.32–16 μM) stimulation of phospholipase A2(PLA2) activity resulting in the increased release of free arachidonic acid from exogenous [1-14C]phosphatidylcholine (PC). The potencies of the cannabinoids in modulating PLA2activity were approximately of the order: 7-OH-Δ1-THC > Δ1-THC > 7-oxo-Δ1-THC > Δ1-THC-7oic acid = 6α OH-Δ1-THC ≫ 6β-OH-Δ1-THC. The hydrolysis of phosphatidylinositol (PI) by synaptosomal phospholipase C (PLC) was enhanced significantly by Δ1-THC and promoted diacylglyceride levels by greater than 100 percent compared to control values. In contrast, arachidonate was the major product resulting from phospholipase activities of a 20,000gpellet. Synaptosomal diacylglyceride lipase activity was inhibited by Δ1-THC. [1-14C]Arachidonic acid was readily incorporated into subcellular membrane phospholipids and after exposure to cannabinoids led to diminished phosphoglyceride levels and concomitant increases in released neutral lipid products. These data suggest that cannabinoids control phospholipid turnover and metabolism in mouse brain preparations by the activation of phospholipases and, through this mechanism, may exert some of their effects.