有机磷抗胆碱酯酶并非通过抑制脑啡肽降解来介导镇痛作用。

Organophosphorus anticholinesterases do not mediate analgesia through inhibition of enkephalin degradation.

作者信息

Marchner H, Haraldsson S, Lundberg S

出版信息

Life Sci. 1986 Apr 7;38(14):1317-21. doi: 10.1016/0024-3205(86)90426-1.

Abstract

The effect on enkephalin degradation of the four highly potent organophosphorus anticholinesterases, soman, sarin, tabun and DFP was studied in synaptosomal fractions of rat brain striata. None of the agents effected any of the enkephalin degrading enzymes, the puromycin sensitive aminopeptidase, the p-hydroxymercurybenzoate (p-HMB) sensitive dipeptidyl aminopeptidase or the phosphoramidon sensitive enkephalinase. Furthermore, no peptidase function of acetylcholinesterase was found, when Leu-enkephalin was used as substrate at low concentrations (27 nM). Supporting the in vitro data, no difference was obtained in the striatal levels of Met- and Leu-enkephalin between rats receiving a high single dose of soman and controls. The results show that the analgesic effect of anticholinesterases are more likely due to mechanisms other than inhibition of enkephalin degradation.

摘要

研究了四种高效有机磷抗胆碱酯酶——梭曼、沙林、塔崩和二异丙基氟磷酸酯（DFP）对大鼠脑纹状体突触体部分脑啡肽降解的影响。这些药剂均未对任何脑啡肽降解酶、嘌呤霉素敏感的氨肽酶、对羟基汞苯甲酸（p-HMB）敏感的二肽基氨肽酶或磷酰胺素敏感的脑啡肽酶产生影响。此外，当低浓度（27 nM）亮脑啡肽用作底物时，未发现乙酰胆碱酯酶具有肽酶功能。与体外实验数据相符，接受高剂量单次梭曼注射的大鼠与对照组相比，纹状体内甲硫氨酸脑啡肽和亮脑啡肽水平并无差异。结果表明，抗胆碱酯酶的镇痛作用更可能是由抑制脑啡肽降解以外的机制所致。