Department of Pharmacology (INFAR), Universidade Federal de São Paulo, Rua Três de Maio 100, São Paulo, SP, Brazil.
Chem Biol Interact. 2010 Jun 7;186(1):9-15. doi: 10.1016/j.cbi.2010.04.002. Epub 2010 May 5.
The role of acetylcholinesterase (AChE) in the termination of the cholinergic response through acetylcholine (ACh) hydrolysis and the involvement of plasma butyrylcholinesterase (BuChE), mainly of hepatic origin, in the metabolism of xenobiotics with ester bonds is well known. Besides, BuChE has a crucial role in ACh hydrolysis, especially when selective anticholinesterases inhibit AChE. Herein, we analyzed the gender-related differences and the circadian changes of rat plasma cholinesterases. Plasma and liver cholinesterase activities were evaluated in control or 2-30-day castrated adult male and female rats. Plasma and liver AChE activities did not differ between genders and were not influenced by sex hormone deprivation. BuChE plasma activity was 7 times greater in female, reflecting gender differences in liver enzyme expression. Castration increased liver and plasma BuChE activity in male, while reduced it in female, abolishing gender differences in enzyme activity. Interestingly, female AChE and BuChE plasma activities varied throughout the day, reaching values 27% and 42% lower, respectively, between 2 p.m. and 6 p.m. when compared to the morning peaks at 8 a.m. Castration attenuated daily female BuChE oscillation. On the other hand, male plasma enzymes remained constant throughout the day. In summary, our results show that liver and plasma BuChE, but not AChE, expression is influenced by sex hormones, leading to high levels of blood BuChE in females. The fluctuation of female plasma BuChE during the day should be taken into account to adjust the bioavailability and the therapeutic effects of cholinesterase inhibitors used in cholinergic-based conditions such Alzheimer's disease.
乙酰胆碱酯酶 (AChE) 通过水解乙酰胆碱 (ACh) 来终止胆碱能反应，以及主要来源于肝脏的血浆丁酰胆碱酯酶 (BuChE) 在酯键类外来化合物的代谢中的作用是众所周知的。此外，BuChE 在 ACh 水解中起着至关重要的作用，特别是当选择性抗胆碱酯酶抑制 AChE 时。在此，我们分析了大鼠血浆胆碱酯酶的性别相关差异和昼夜变化。在对照或 2-30 天去势成年雄性和雌性大鼠中评估了血浆和肝脏胆碱酯酶的活性。性别之间的血浆和肝脏 AChE 活性没有差异，也不受性激素剥夺的影响。雌性的 BuChE 血浆活性高 7 倍，反映了肝脏酶表达的性别差异。去势增加了雄性大鼠的肝脏和血浆 BuChE 活性，而降低了雌性大鼠的活性，消除了酶活性的性别差异。有趣的是，雌性 AChE 和 BuChE 血浆活性在一天中变化，与上午 8 点的峰值相比，下午 2 点至 6 点之间分别降低了 27%和 42%。去势减弱了雌性 BuChE 的昼夜波动。另一方面，雄性血浆酶在一天中保持不变。总之，我们的结果表明，肝脏和血浆 BuChE，但不是 AChE 的表达受性激素影响，导致女性血液 BuChE 水平升高。在基于胆碱能的疾病（如阿尔茨海默病）中，应考虑女性血浆 BuChE 全天波动，以调整胆碱酯酶抑制剂的生物利用度和治疗效果。
