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鞘内注射针对内源性阿片肽的抗血清对小鼠一氧化二氮镇痛作用的拮抗作用。

Antagonism of nitrous oxide antinociception in mice by intrathecally administered antisera to endogenous opioid peptides.

作者信息

Cahill F J, Ellenberger E A, Mueller J L, Tseng L F, Quock R M

机构信息

Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, IL, USA.

出版信息

J Biomed Sci. 2000 Jul-Aug;7(4):299-303. doi: 10.1007/BF02253248.

DOI:10.1007/BF02253248
PMID:10895052
Abstract

Previously it was demonstrated that nitrous oxide antinociception in the mouse abdominal constriction test is mediated by kappa-opioid receptors. Since nitrous oxide is thought to cause the neuronal release of endogenous opioid peptide to stimulate opioid receptors, this study was designed to identify the opioid peptides involved, especially in the spinal cord, by determining whether nitrous oxide antinociception can be differentially inhibited by intrathecally (i. t.) administered antisera to different opioid peptides. Male NIH Swiss mice were pretreated i.t. with rabbit antisera to opioid peptides then exposed 24 h later to one of three different concentrations of nitrous oxide in oxygen. Dose-response curves constructed from the data indicated that the antinociceptive effect of nitrous oxide was significantly antagonized by antisera to various dynorphins (DYNs) and methionine-enkephalin (ME), but not by antiserum to beta-endorphin (beta-EP). The AD(50) values for nitrous oxide antinociception were significantly elevated by antisera to DYNs and ME but not beta-EP. These findings of this study support the hypothesis that nitrous oxide antinociception in the mouse abdominal constriction test involves the neuronal release of DYN and ME in the spinal cord.

摘要

先前的研究表明,在小鼠腹部收缩试验中,一氧化二氮的抗伤害感受作用是由κ-阿片受体介导的。由于一氧化二氮被认为可引起内源性阿片肽的神经元释放以刺激阿片受体,本研究旨在通过确定鞘内注射针对不同阿片肽的抗血清是否能差异性地抑制一氧化二氮的抗伤害感受作用,来鉴定所涉及的阿片肽,尤其是脊髓中的阿片肽。雄性NIH瑞士小鼠经鞘内注射针对阿片肽的兔抗血清进行预处理,然后在24小时后暴露于三种不同浓度的一氧化二氮与氧气的混合气中。根据数据构建的剂量-反应曲线表明,一氧化二氮的抗伤害感受作用被针对各种强啡肽(DYNs)和甲硫氨酸脑啡肽(ME)的抗血清显著拮抗,但未被针对β-内啡肽(β-EP)的抗血清拮抗。针对DYNs和ME的抗血清可使一氧化二氮抗伤害感受作用的半数有效剂量(AD50)值显著升高,但针对β-EP的抗血清则无此作用。本研究的这些发现支持了以下假说:在小鼠腹部收缩试验中,一氧化二氮的抗伤害感受作用涉及脊髓中DYN和ME的神经元释放。

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