Imidazoline receptor antisera‐selected/Nischarin regulates the effect of agmatine on the development of morphine dependence
Imidazoline receptor antisera‐selected/Nischarin regulates the effect of agmatine on the development of morphine dependence
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DOI：
10.1111/j.1369-1600.2011.00373.x
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发表时间：
2012-03
影响因子：
3.4
通讯作者：
Fei Li;N. Wu;R. Su;Ying Chen;Xin-qiang Lu;Yin Liu;Jin Li
中科院分区：
文献类型：
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作者：
Fei Li;N. Wu;R. Su;Ying Chen;Xin-qiang Lu;Yin Liu;Jin Li
胍丁胺是咪唑啉受体的内源性配体，已被证明可预防阿片类药物依赖，但其作用机制尚不清楚。本研究从药理学和分子生物学的角度探讨了I1咪唑啉受体及其候选蛋白咪唑啉受体抗血清选择性抗体（IRAS）/Nischarin在吗啡依赖中的作用以及胍丁胺对吗啡依赖的抑制作用。结果表明，在基础条件下，抑制IRAS或Nischarin并不改变吗啡依赖的体外和体内发展。胍丁胺在0.01-10 μM浓度下可减少原代培养大鼠海马神经元环磷酸腺苷（cAMP）超射，在5 mg/kg剂量下可减弱吗啡依赖小鼠的戒断信号和FosB及ΔFosB的升高。胍丁胺的作用被efaroxan（I1咪唑啉受体非特异性拮抗剂）和针对IRAS或Nischarin的RNA干扰所抑制。这些结果表明I1咪唑啉受体或IRAS/Nischarin介导胍丁胺对吗啡依赖的作用，为I1咪唑啉受体可能成为治疗吗啡依赖的新靶点提供了证据。
Agmatine, an endogenous ligand for imidazoline receptor, has been shown to prevent opioid dependence, but not much is known about the mechanisms of the effect of agmatine. In the present study, we investigated the function of I1 imidazoline receptor and its candidate protein imidazoline receptor antisera‐selected (IRAS)/Nischarin in morphine dependence as well as in the effect of agmatine inhibiting morphine dependence by pharmacological and molecular approaches. Results showed that inhibition of IRAS or Nischarin did not change the development of morphine dependence in vitro and in vivo under the basal condition. Agmatine could reduce the cyclic 3′, 5′ adenosine monophosphate (cAMP) overshoot at the concentration of 0.01–10 µM in the primary cultured rat hippocampal neurons and attenuated the withdrawal signals and the elevation of FosB and ΔFosB at the dose of 5 mg/kg in the morphine‐dependent mice. The effect of agmatine was inhibited by efaroxan (I1 imidazoline receptor non‐specific antagonist) and the RNA interference against IRAS or Nischarin. These findings indicate that I1 imidazoline receptor or IRAS/Nischarin mediates the effect of agmatine on morphine dependence and provide evidence that I1 imidazoline receptor may be a new target for treating morphine dependence.