Department of Clinical Pharmacy, School of Pharmacy, Zunyi Medical University, Zunyi, China.
Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, China.
J Pharm Pharmacol. 2020 Nov;72(11):1556-1563. doi: 10.1111/jphp.13341. Epub 2020 Aug 2.
To determine whether ecto-5'-nucleotidase (e5NT) contributes to the release of adenosine and uridine and whether is establishes the role of e5NT in acute restraint stress-induced depression and anxiety-like behaviours in mice.
Acute restraint stress was induced to detect the level of nucleoside in the hippocampus. Mouse hippocampal brain proteins were isolated and subjected to Western blotting (WB) experiments to examine the protein expression levels of proteins that affect nucleoside release. Adenosine 5'-(α,β-methylene)diphosphate (APCP), an e5NT inhibitor, was intraventricularly injected to investigate the regulatory effect of e5NT on nucleoside levels and behavioural changes caused by acute restraint stress in mice.
Acute restraint stress increased the level of extracellular adenosine and uridine levels in the hippocampus of mice and significantly increased the expression of extracellular nucleoside-metabolizing enzymes were significantly increased. By administering APCP, the increase in adenosine and uridine levels caused by acute restraint stress could be suppressed. APCP inhibited behavioural changes, which were induced by acute restraint stress.
These data suggest that acute restraint stress may alter extracellular adenosine and uridine levels content in the hippocampus of mice via e5NT, and thus, the inhibition of e5NT may improve the anxiety behaviour in mice. Therefore, e5NT may therefore be a potential therapeutic target for the treatment of anxiety in mice.
确定外核苷酸酶 5'（e5NT）是否有助于腺苷和尿苷的释放，以及它是否在急性束缚应激诱导的小鼠抑郁和焦虑样行为中建立 e5NT 的作用。
诱导急性束缚应激以检测海马中的核苷水平。分离小鼠海马脑蛋白，并进行 Western blot（WB）实验，以检查影响核苷释放的蛋白质的蛋白表达水平。外核苷酸酶 5'（α，β-亚甲基）二磷酸（APCP）是一种 e5NT 抑制剂，被脑室注射，以研究 e5NT 对急性束缚应激引起的小鼠核苷水平和行为变化的调节作用。
急性束缚应激增加了小鼠海马中外周腺苷和尿苷水平，并显著增加了细胞外核苷代谢酶的表达。通过给予 APCP，可抑制急性束缚应激引起的腺苷和尿苷水平升高。APCP 抑制了急性束缚应激诱导的行为变化。
这些数据表明，急性束缚应激可能通过 e5NT 改变小鼠海马中外周腺苷和尿苷水平的含量，因此抑制 e5NT 可能改善小鼠的焦虑行为。因此，e5NT 可能是治疗小鼠焦虑的潜在治疗靶点。
