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核苷酸酶在外核苷酸酶和神经肽-S 对小鼠运动活性的协同作用中的作用。

Role of the ecto-nucleotidases in the cooperative effect of adenosine and neuropeptide-S on locomotor activity in mice.

机构信息

Laboratório de Neurociências, Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.

出版信息

Pharmacol Biochem Behav. 2011 Oct;99(4):726-30. doi: 10.1016/j.pbb.2011.06.028. Epub 2011 Jul 1.

DOI:10.1016/j.pbb.2011.06.028
PMID:21741987
Abstract

Activation of adenosine receptors modifies the action of classic neurotransmitters (i.e. dopamine, glutamate and acetylcholine) and other neuromodulators, like vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP) and neuropeptide S (NPS). Similarly to adenosine, NPS is involved in the regulation of stimulus and response to fear and arousal. Thus, the present study investigates the effects of NPS on locomotor activity in mice treated with or without α,β-methylene adenosine 5'-diphosphate (AOPCP), the inhibitor of ecto-5'-nucleotidase. Additionally, we evaluate the activity of ecto-5'-nucleotidase in brain slices of mice treated with or without NPS. Male adult CF-1 mice received i.c.v. NPS as 0.1 nmol injection with or without pre-treatment with 1 nmol α,β-methylene adenosine 5'-diphosphate (AOPCP), the selective inhibitor of ecto-5'-nucleotidase, to evaluate locomotor activity. In another set of experiments, mice received i.c.v. infusion of 0.1 nmol NPS to assay enzymatic activity in brain slices. The results demonstrated that the pre-treatment with AOPCP, which was inactive per se, prevented NPS-induced hyperlocomotion in mice. The dose of 0.1 nmol NPS was efficient to induce hyperlocomotion in animals during the observation period in the activity cage. Regarding enzymatic activity, i.c.v. NPS injection did not induce any significant alterations in ATP and AMP hydrolysis in striatum and hippocampus brain slices of mice. The present study shows that the hyperlocomotor effect of NPS depends on the ecto-5'-nucleotidase activity.

摘要

腺苷受体的激活可调节经典神经递质(如多巴胺、谷氨酸和乙酰胆碱)和其他神经调质(如血管活性肠肽(VIP)、降钙素基因相关肽(CGRP)和神经肽 S(NPS))的作用。与腺苷类似,NPS 参与了对恐惧和觉醒的刺激和反应的调节。因此,本研究调查了 NPS 对接受或未接受外核苷酸酶抑制剂 α,β-亚甲基腺苷 5'-二磷酸(AOPCP)处理的小鼠的运动活性的影响。此外,我们还评估了接受或未接受 NPS 处理的小鼠脑切片中外核苷酸酶的活性。雄性成年 CF-1 小鼠接受侧脑室注射 0.1 nmol NPS,同时或预先用 1 nmol α,β-亚甲基腺苷 5'-二磷酸(AOPCP)处理,该物质是外核苷酸酶的选择性抑制剂,以评估运动活性。在另一组实验中,小鼠接受侧脑室输注 0.1 nmol NPS,以检测脑切片中的酶活性。结果表明,本身无活性的 AOPCP 预处理可防止 NPS 诱导的小鼠过度活跃。0.1 nmol NPS 的剂量可有效地诱导动物在活动笼中的观察期内过度活跃。关于酶活性,侧脑室注射 NPS 不会引起小鼠纹状体和海马脑切片中 ATP 和 AMP 水解的任何显著变化。本研究表明,NPS 的过度活跃效应取决于外核苷酸酶的活性。

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