Abolished thermal and mechanical antinociception but retained visceral chemical antinociception induced by butorphanol in μ-opioid receptor knockout mice
Abolished thermal and mechanical antinociception but retained visceral chemical antinociception induced by butorphanol in μ-opioid receptor knockout mice
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DOI：
10.1016/j.neuropharm.2008.03.008
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发表时间：
2008-06-01
影响因子：
4.7
通讯作者：
Ikeda, Kazutaka
中科院分区：
文献类型：
--
作者：
Ide, Soichiro;Minami, Masabumi;Ikeda, Kazutaka
布托啡诺被假设为通过阿片途径诱导镇痛，尽管其作用的确切机制尚不清楚。在这项研究中，我们研究了μ阿片受体（MOP）在布托啡诺诱导的热，机械和内脏化学抗伤害感受中的作用，使用MOP敲除（KO）小鼠。布托啡诺诱导的热镇痛，评估热板和甩尾试验，显着减少杂合子和纯合子MOP-KO小鼠与野生型小鼠相比，废除。从我们的布托啡诺诱导的机械性抗伤害性实验中获得的结果，由Randall-Selitto测试评估，从这些小鼠的热抗伤害性实验中获得的结果相似。然而，有趣的是，布托啡诺在纯合子MOP-KO小鼠中保留了诱导显著内脏化学镇痛的能力，通过扭体试验进行评估。纯合MOP-KO小鼠中保留的布托啡诺诱导的内脏化学抗伤害感受可通过K阿片受体（KOP）拮抗剂nor-binaltorphimine预处理完全阻断。体外结合和环磷酸腺苷测定也表明布托啡诺对KOP和MOPs的亲和力高于δ阿片受体。这些结果分子生物学证实了先前的研究涉及MOPs，部分KOP，在介导布托啡诺诱导的镇痛。(c)2008爱思唯尔有限公司保留所有权利。
Butorphanol is hypothesized to induce analgesia via opioid pathways, although the precise mechanisms for its effects remain unknown. In this study, we investigated the role of the mu-opioid receptor (MOP) in thermal, mechanical, and visceral chemical antinociception induced by butorphanol using MOP knockout (KO) mice. Butorphanol-induced thermal antinociception, assessed by the hot-plate and tail-flick tests, was significantly reduced in heterozygous and abolished in homozygous MOP-KO mice compared with wildtype mice. The results obtained from our butorphanol-induced mechanical antinociception experiments, assessed by the Randall-Selitto test, were similar to the results obtained from the thermal antinociception experiments in these mice. Interestingly, however, butorphanol retained its ability to induce significant visceral chemical antinociception, assessed by the writhing test, in homozygous MOP-KO mice. The butorphanol-induced visceral chemical antinociception that was retained in homozygous MOP-KO mice was completely blocked by pretreatment with nor-binaltorphimine, a K-Opioid receptor (KOP) antagonist. In vitro binding and cyclic adenosine monophosphate assays also showed that butorphanol possessed higher affinity for KOPs and MOPs than for delta-opioid receptors. These results molecular pharmacologically confirmed previous studies implicating MOPs, and partially KOPs, in mediating butorphanol-induced analgesia. (c) 2008 Elsevier Ltd. All rights reserved.