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首页> 外文期刊>The Journal of toxicological sciences >Roles of mu-opioid receptors in development of tolerance to diisopropylfluorophosphate (DFP).
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Roles of mu-opioid receptors in development of tolerance to diisopropylfluorophosphate (DFP).

机译：mu阿片受体在对二异丙基氟磷酸盐（DFP）耐受性发展中的作用。

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Anatomical evidence indicates that cholinergic and opioidergic systems are co-localized and acting on the same neuron. However, the regulatory mechanisms between cholinergic and opioidergic system have not been well characterized. In the present study, the potential involvement of mu-opioid receptors in mediating the changes of toxic signs and muscarinic receptor binding after administration of irreversible anti-acetylcholinesterase diisopropylfluorophosphate (DFP) was investigated. DFP (1 mg/kg/day, subcutaneous injection, s.c.)-induced tremors and chewing movements were monitored during the 28-day treatment period in mu-opioid receptor knockout and wild type mice. Autoradiographic studies of total, M1, and M2 muscarinic receptors were conducted using [(3)H]-quinuclidinyl benzilate, [(3)H]-pirenzepine, and [(3)H]-AF-DX384 as ligands, respectively. DFP-induced tremors in both mu-opioid receptor knockout and wild type mice showed tolerance development. However, DFP-induced tremors in mu-opioid receptor knockout mice showed delayed tolerance development than that of DFP-treated wild type controls. DFP-induced chewing movements in both mu-opioid receptor knockout and wild type mice failed to show development of tolerance after four weeks of treatment. M2 muscarinic receptor binding of DFP-treated mu-opioid receptor knockout mice was significantly decreased than that of the DFP-treated wild type controls in the striatum, but not in the cortex and hippocampus. However, there were no significant differences in total and M1 muscarinic receptor binding between DFP-treated mu-opioid receptor knockout and wild type mice in the cortex, striatum and hippocampus. These studies indicate that mu-opioid receptors play an important role through the striatal M2 muscarinic receptors to regulate the development of tolerance to DFP-induced tremors.
机译：解剖学证据表明，胆碱能和视皮醇能系统共同定位并作用于同一神经元。但是，胆碱能和卵磷脂系统之间的调节机制尚未很好地表征。在本研究中，研究了在给予不可逆的抗乙酰胆碱酯酶二异丙基氟磷酸酯（DFP）后，μ阿片受体可能参与介导毒性体征和毒蕈碱受体结合的变化。在μ阿片受体敲除和野生型小鼠的28天治疗期间，监测了DFP（1mg / kg /天，皮下注射，皮下注射）引起的震颤和咀嚼运动。分别使用[（3）H]-奎宁环烷基苯甲酸酯，[（3）H]-哌仑西平和[（3）H] -AF-DX384作为配体进行总，M1和M2毒蕈碱受体的放射自显影研究。在μ阿片受体敲除和野生型小鼠中DFP引起的震颤均显示出耐受性的发展。但是，与DFP处理的野生型对照相比，μ阿片受体敲除小鼠中DFP引起的震颤显示出延迟的耐受性发展。在治疗四周后，在阿片类受体受体敲除和野生型小鼠中DFP诱导的咀嚼运动均未显示出耐受性的发展。在纹状体中，DFP处理的类阿片受体敲除小鼠的M2毒蕈碱受体结合显着低于DFP处理的野生型对照，但在皮质和​​海马中没有。但是，在皮质，纹状体和海马体中，DFP处理的阿片类受体受体敲除与野生型小鼠之间的总和M1毒蕈碱受体结合没有显着差异。这些研究表明，μ阿片受体通过纹状体M2毒蕈碱受体在调节DFP诱导的震颤耐受性的发展中起重要作用。

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