The role of IRAS/Nischarin involved in the development of morphine tolerance and physical dependence.
The role of IRAS/Nischarin involved in the development of morphine tolerance and physical dependence.
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IRAS/Nischarin 的作用涉及吗啡耐受性和身体依赖性的发展。
DOI：
10.1016/j.bbrc.2019.03.055
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发表时间：
2019-05
期刊：
影响因子：
--
通讯作者：
李锦
中科院分区：
文献类型：
--
作者：
李硕;吴宁;赵太云;卢关伊;王志媛;李斐;李锦
吗啡是一种有效的阿片类镇痛药，用于缓解中度或重度疼痛，但药物耐受性和依赖性的发展限制了其在疼痛管理中的使用。我们前期的研究表明，I1咪唑啉受体的候选蛋白--咪唑啉受体抗血清选择性（IRAS）/Nischarin与μ阿片受体（莫尔）相互作用并调节其转运。然而，还没有关于IRAS对吗啡耐受和身体依赖的影响的报道。在本研究中，我们发现，IRAS敲除（KO）小鼠表现出加剧的镇痛耐受性和身体依赖性相比，野生型（WT）小鼠慢性吗啡治疗。长期吗啡处理可下调IRAS KO小鼠脊髓莫尔的表达，而对WT小鼠脊髓莫尔的表达无明显影响。我们观察到吗啡耐受后脊髓cAMP的代偿性增加，KO小鼠的这种变化比WT小鼠更明显。此外，KO小鼠表现出更多的AMPA受体GluR 1-S845磷酸化的升高比WT小鼠，而GluR 1的总表达量在吗啡依赖后保持不变。这些结果提示，IRAS可能通过调节莫尔的表达和AMPA GluR 1-S845的磷酸化，在体内吗啡耐受和身体依赖的形成中发挥重要作用，这可能是阿片成瘾形成的机制之一。
Morphine is a potent opioid analgesic used to alleviate moderate or severe pain, but the development of drug tolerance and dependence limits its use in pain management. Our previous studies showed that the candidate protein for I1 imidazoline receptor, imidazoline receptor antisera-selected (IRAS)/Nischarin, interacts with μ opioid receptor (MOR) and modulates its trafficking. However, there is no report of the effect of IRAS on morphine tolerance and physical dependence. In the present study, we found that IRAS knockout (KO) mice showed exacerbated analgesic tolerance and physical dependence compared to wild-type (WT) mice by chronic morphine treatment. Chronic morphine treatment down-regulated the expression of MOR in spinal cord of IRAS KO mice, while had no significant effect on MOR expression in WT mice. We observed the compensatory increase of cAMP accumulation in spinal cord after morphine tolerance, and this change was more significant in KO mice than WT mice. Furthermore, KO mice showed more elevation in the phosphorylation of AMPA receptor GluR1-S845 than WT mice, while the total expression of GluR1 remained unchanged after morphine dependence. Altogether, these data suggest that IRAS may play an important role in the development of morphine tolerance and physical dependence in vivo through modulating MOR expression, as well as AMPA GluR1-S845 phosphorylation, which might be one of the mechanisms underlying the development of opiate addiction.
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影响因子：
3.4
作者：
Oh, Jeong Hwan;Yang, Ju Hwan;Choe, Eun Sang
通讯作者：
Choe, Eun Sang
DOI：
--
发表时间：
1988-09
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
R. Duman;J. Tallman;Eric J. Nestler
通讯作者：
R. Duman;J. Tallman;Eric J. Nestler
影响因子：
5
作者：
R. Su;Xin-qiang Lu;Yu Huang;Yin Liu;Zheng-hua Gong;Xiaocui Wei;N. Wu;Jin Li
通讯作者：
R. Su;Xin-qiang Lu;Yu Huang;Yin Liu;Zheng-hua Gong;Xiaocui Wei;N. Wu;Jin Li
影响因子：
16.2
作者：
Ehlers, MD
通讯作者：
Ehlers, MD
内源性褪黑素能系统在大鼠慢性吗啡引起的痛觉过敏和耐受性发展中的作用
影响因子：
3.8
作者：
Fan, Yuchao;Liang, Xiao;Song, Li
通讯作者：
Song, Li