Antagonism of the antinociceptive effect of nitrous oxide by inhibition of enzyme activity or expression of neuronal nitric oxide synthase in the mouse brain and spinal cord.

Antagonism of the antinociceptive effect of nitrous oxide by inhibition of enzyme activity or expression of neuronal nitric oxide synthase in the mouse brain and spinal cord.
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一氧化二氮通过抑制酶活性或在小鼠脑和脊髓中神经元一氧化氮合酶表达的抗伤害感受作用的拮抗作用。

DOI:
10.1016/j.ejphar.2009.09.059
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发表时间:
2010-01-25
影响因子:
5
通讯作者:
Quock, Raymond M.
Quock, Raymond M.
中科院分区:
医学2区
文献类型:
--
作者:
Cope, Jessica Lack;Chung, Eunhee;Ohgami, Yusuke;Quock, Raymond M.

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以前的研究表明,一氧化氮(NO)参与了麻醉气体一氧化二氮(N2O)的抗伤害反应。本研究通过药理学和基因敲除和敲除策略来抑制脊髓上和脊髓中NO的产生,以证实这种NO的参与。在NIH瑞士小鼠侧脑室注射(i.c.v)后,用冰醋酸(0.6%)腹部收缩试验评估对70%N2O的抗伤害反应。或鞘内(I.T.)预先给予一氧化氮合酶抑制剂L-NG-硝基精氨酸甲酯(L-NAME)或针对神经元型一氧化氮合酶(NNOS)的反义寡核苷酸(AS-ODN)。实验也在nNOS基因(nNOS−/−)纯合的小鼠身上进行。经静脉注射预处理的小鼠。或IT。使用L-NAME(1.0μg)时,两者均使N2O引起的抗伤害反应幅度降低80-90%。经静脉注射预处理的小鼠。或IT。以一氧化氮合酶为底物的反义寡核苷酸(3×25μg)对伤害性反应的拮抗率为60-80%。与野生型小鼠相比,nNOS基因敲除小鼠在N2O诱导的抗伤害感受方面减少了60%。这些发现一致表明,nNOS表达的短暂或发育性抑制显著降低了对N2O的抗伤害性反应。因此,脊髓上和脊髓来源的NO在N2O的抗伤害性反应中起着重要作用。
Previous studies have implicated nitric oxide (NO) in the antinociceptive response to the anesthetic gas nitrous oxide (N2O). The present study was conducted to confirm this NO involvement using pharmacological and gene knockdown and knockout strategies to inhibit the supraspinal and spinal production of NO. Antinociceptive responsiveness to 70% N2O was assessed using the acetic acid (0.6%) abdominal constriction test in NIH Swiss mice following intracerebroventricular (i.c.v.) or intrathecal (i.t.) pretreatment with the NOS-inhibitor L-NG-nitro arginine methyl ester (L-NAME) or an antisense oligodeoxynucleotide (AS-ODN) directed against neuronal NOS (nNOS). Experiments were also conducted in mice homozygous for a defective nNOS gene (nNOS−/−). Mice that were pretreated i.c.v. or i.t. with L-NAME (1.0 μg) both exhibited 80-90% reduction in the magnitude of the N2O-induced antinociceptive response. Mice that were pretreated i.c.v. or i.t. with nNOS AS-ODN (3×25 μg) exhibited a 60-80% antagonism of the antinociceptive response. Compared to wild-type mice, nNOS knockout mice showed a 60% reduction in N2O-induced antinociception. These findings consistently demonstrate that transient or developmental suppression of nNOS expression significantly reduces antinociceptive responsiveness to N2O. NO of both supraspinal and spinal origin, therefore, plays an important role in the antinociceptive response to N2O.
DOI: 10.1016/0006-8993(95)00065-x
发表时间: 1995-03-27
期刊: BRAIN RESEARCH
影响因子: 2.9
作者:
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DOI: 10.1111/j.1476-5381.1957.tb01354.x
发表时间: 1957-01-01
期刊: BRITISH JOURNAL OF PHARMACOLOGY AND CHEMOTHERAPY
影响因子: --
作者:
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