Dynorphin B and spinal analgesia:: induction of antinociception by the cannabinoids CP55,940, Δ9-THC and anandamide
Dynorphin B and spinal analgesia:: induction of antinociception by the cannabinoids CP55,940, Δ9-THC and anandamide
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DOI：
10.1016/s0006-8993(00)01981-8
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发表时间：
2000-02-28
期刊：
影响因子：
2.9
通讯作者：
Welch, SP
中科院分区：
文献类型：
--
作者：
Houser, SJ;Eads, M;Welch, SP
内源性阿片样物质dynorphin B在大麻素诱导的抗痛觉作用中被评价。我们实验室之前的工作表明，合成的双环大麻素CP55,940诱导释放肌啡肽B，而天然存在的大麻素Delta(9)-四氢大麻酚（Delta(9)-THC）释放肌啡肽a。肌啡肽在一定程度上有助于脊髓水平上两种大麻素的抗伤害性作用。本研究比较了灌注大鼠脊髓在急性给药后10分钟和30分钟两个时间点(anandamide （AEA), Delta(9)-THC和CP55,940）释放的dynorphin B，并试图将这种释放与药物的抗伤害感受作用联系起来。从Delta(9)-THC、CP55,940或AEA预处理的大鼠脊髓灌注液中收集Dynorphin B。将上清液冻干，用放射免疫法测定dynorphin B的浓度。在抗痛觉的高峰时间（10 min）， CP55,940和Delta(9)-THC诱导dynorphin B的释放显著增加2倍。AEA不显著释放dynorphin B。药物预处理30 min后，虽然CP55,940和Delta(9)-THC的抗痛觉作用持续存在，但未观察到dynorphin B的显著释放。先前的研究表明，Delta(9)-THC释放dynorphin A，而AEA不释放dynorphin A。本研究证实，虽然三种试验药物均在10 min时产生显著的抗痛觉作用，但内源性大麻素AEA并不通过释放dynorphin诱导抗痛觉作用。因此，我们的数据表明了一种独特的机制，它是aea诱导的抗痛觉的基础。(C) 2000 Elsevier Science B.V.版权所有
The endogenous opioid dynorphin B was evaluated for its role in cannabinoid-induced antinociception. Previous work in our laboratory has shown that the synthetic, bicyclic cannabinoid, CP55,940, induces the release of dynorphin B whilst the naturally occurring cannabinoid, Delta(9)-tetrahydrocannabinol (Delta(9)-THC), releases dynorphin A. The dynorphins contribute in part to the antinociceptive effects of both cannabinoids at the level of the spinal cord. The present study compares dynorphin B released from perfused rat spinal cord in response to acute administration of anandamide (AEA), Delta(9)-THC and CP55,940 at two time points, 10 min and 30 min post administration, and attempts to correlate such release with antinociceptive effects of the drugs. Dynorphin B was collected from spinal perfusates of rats pretreated with Delta(9)-THC, CP55,940 or AEA. The supernatant was lyophilized and the concentrations of dynorphin B were measured via radioimmunoassay. At a peak time of antinociception (10 min), CP55,940 and Delta(9)-THC induced significant two-fold increases in the release of dynorphin B. AEA did not significantly release dynorphin B. Upon a 30-min pretreatment with the drugs, no significant dynorphin B release was observed, although antinociceptive effects persisted for CP55,940 and Delta(9)-THC. Previous work indicates that Delta(9)-THC releases dynorphin A while AEA releases no dynorphin A. This study confirms that although all three test drugs produced significant antinociception at 10 min, the endocannabinoid, AEA, does not induce antinociception via dynorphin release. Thus, our data indicate a distinct mechanism which underlies AEA-induced antinociception. (C) 2000 Elsevier Science B.V. All rights reserved.