Intrathecal pertussis toxin treatment attenuates opioid antinociception and reduces high-affinity state of opioid receptors.
Intrathecal pertussis toxin treatment attenuates opioid antinociception and reduces high-affinity state of opioid receptors.
复制标题
鞘内百日咳毒素治疗可减弱阿片类药物的镇痛作用并降低阿片类药物受体的高亲和力状态。
DOI：
10.1097/00000542-199210000-00013
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发表时间：
1992
期刊：
影响因子：
8.8
通讯作者：
Watkins,WD
中科院分区：
文献类型：
--
作者：
Wong,CS;Su,YF;Chang,KJ;Watkins,WD
研究百日咳毒素对大鼠阿片类药物抗痛觉作用的影响。鞘内注射单剂量百日咳毒素会以剂量和时间依赖的方式降低PL017（一种高度选择性的多阿片受体激动剂）的抗痛感作用。百日咳毒素的最大有效剂量为1微克，在第3天达到最大效果。毒素作用持续2周，第3周抗伤感受反应部分恢复。随着百日咳毒素剂量的增加，PL017抗伤感受作用的剂量-反应曲线向右偏移。注射百日咳3天后，脊髓腰骶段膜的受体结合活性下降到对照组的70%，125I-FK33824是一种高选择性的受体激动剂。在以[3H]纳洛酮为放射性标记配体的实验中，百日咳毒素处理后FK33824的位移曲线右移。这种变化也与剂量和时间有关。结合数据的Scatchard分析显示，百日咳毒素处理后，结合位点的总数没有明显变化，但在高亲和力位点之外出现了一类低亲和力的结合位点。当脊髓膜在Na+(100 mM)和鸟苷二磷酸（100微米）中洗涤，并在Mg2+(5 mM)存在下检测结合时，所有mu受体在对照膜中都处于高亲和力状态。百日咳毒素处理后，低亲和位点与高亲和位点的比例增加。（摘要删节250字）
The effect of pertussis toxin on opioid antinociception was studied in rats. Intrathecal injection of a single dose of pertussis toxin reduced the antinociceptive effect of PL017, a highly selective mu-opioid agonist, in a dose-and time-dependent manner. The maximal effective dose of pertussis toxin was 1 microgram, and the maximal effect was seen at day 3. The effect of the toxin lasted for 2 weeks, and the antinociceptive response recovered partially at the third week. The dose-response curves of the antinociceptive effect of PL017 were shifted to the right with increasing doses of pertussis toxin. Three days after pertussis injection, receptor-binding activity of membranes in the lumbosacral segment of spinal cords decreased to 70% of control as assayed by 125I-FK33824, a highly selective mu-receptor agonist. In experiments using [3H] naloxone as the radiolabeled ligand, displacement curves of FK33824 were shifted to the right after pertussis toxin treatment. The shift also was dose and time dependent. Scatchard analysis of binding data showed that, after pertussis toxin treatment, there was no significant change in the total number of binding sites, but a class of low-affinity binding sites appeared in addition to the high-affinity sites. When spinal membranes were washed in Na+(100 mM) and guanosine diphosphate (100 microM) and binding was assayed in the presence of Mg2+(5 mM), all the mu-receptors were in the high-affinity state in control membranes. After the pertussis toxin treatment, the ratio of low-affinity sites to high-affinity sites increased.(ABSTRACT TRUNCATED AT 250 WORDS)