Regulation of G proteins by chronic morphine in the rat locus coeruleus.

Regulation of G proteins by chronic morphine in the rat locus coeruleus.
复制标题

大鼠蓝斑中慢性吗啡对 G 蛋白的调节。

DOI:
10.1016/0006-8993(89)91243-2
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发表时间:
1989
期刊:
影响因子:
2.9
通讯作者:
Tallman,JF
Tallman,JF
中科院分区:
医学3区
文献类型:
--
作者:
Nestler,EJ;Erdos,JJ;Terwilliger,R;Duman,RS;Tallman,JF

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在大鼠蓝斑(LC)研究了G蛋白在阿片类药物慢性作用中的可能作用。LC是一个相对同质的大脑区域,似乎在动物和人类的急性和慢性阿片类药物作用中发挥着重要作用。结果发现,在已知可诱导阿片类药物耐受和依赖状态的条件下,慢性但非急性地用吗啡处理大鼠,可增加百日咳毒素介导的LC中G蛋白的ADP核糖化水平。吗啡诱导的ADP核糖化增加在GO和GO中都发生,并在30倍的NAD浓度范围内观察到。同时用阿片受体拮抗剂纳曲酮治疗大鼠,可阻断吗啡产生这种作用的能力。相比之下,慢性吗啡对百日咳毒素介导的Giand Go其他脑区的ADP核糖化没有影响,包括新纹状体、额叶皮质和中缝背侧。慢性吗啡对霍乱毒素介导的LC和其他脑区GDP核糖化也没有影响。初步的免疫印迹分析显示,在LC中GOα亚单位的ADP-核糖化水平的增加与该蛋白在该脑区的免疫反应性的等量增加有关。观察到的吗啡对LC中G蛋白的调节可能代表了这些神经元中阿片成瘾的部分变化。
A possible role for G proteins in contributing to the chronic actions of opiates was investigated in the rat locus coeruleus (LC). The LC is a relatively homogeneous brain region that appears to play an important role in mediating acute and chronic opiate action in animals, as well as in humans. It was found that chronic, but not acute, treatment of rats with morphine, under conditions known to induce states of opiate tolerance and dependence, produced an increase in the level of pertussis toxin-mediated ADP-ribosylation of G proteins in the LC. The morphine-induced increase in ADP-ribosylation occured in both Giand Go, and was observed over a 30-fold range of NAD concentrations used. Concomitant treatment of rats with the opiate receptor antagonist naltrexone blocked the ability of morphine to produce this effect. In contrast, chronic morphine had no effect on pertussis toxin-mediated ADP-ribosylation of Giand Goin the other brain regions studied, including the neostriatum, frontal cortex, and dorsal raphe. Chronic morphine also had no effect on cholera toxin-mediated ADP-ribosylation of Gsin the LC and these other brain regions. Preliminary immunoblot analysis revealed that increased ADP-ribosylation levels of the alpha subunit of Goin the LC were associated with equivalent increases in the immunoreactivity of this protein in this brain region. It is possible that the observed regulation of G-proteins by morphine in the LC represents part of the changes that underline opiate addiction in these neurons.
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DOI: 10.1016/0161-4630(80)90090-7
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通过膜调节改变人血小板对花生四烯酸钠的反应。
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DOI: --
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