Houser S J, Eads M, Embrey J P, Welch S P
Department of Nurse Anesthesia, Virginia Commonwealth University, Richmond, VA 23298-0613, USA.
Brain Res. 2000 Feb 28;857(1-2):337-42. doi: 10.1016/s0006-8993(00)01981-8.
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.
对内源性阿片肽强啡肽B在大麻素诱导的镇痛作用中的作用进行了评估。我们实验室之前的研究表明，合成的双环大麻素CP55,940可诱导强啡肽B的释放，而天然存在的大麻素Δ⁹-四氢大麻酚（Δ⁹-THC）则释放强啡肽A。强啡肽在脊髓水平上部分促成了两种大麻素的镇痛作用。本研究比较了在给药后10分钟和30分钟这两个时间点，灌注大鼠脊髓释放的强啡肽B对急性给予花生四烯乙醇胺（AEA）、Δ⁹-THC和CP55,940的反应，并试图将这种释放与药物的镇痛作用相关联。从用Δ⁹-THC、CP55,940或AEA预处理的大鼠脊髓灌流液中收集强啡肽B。将上清液冻干，并通过放射免疫测定法测量强啡肽B的浓度。在镇痛作用的峰值时间（10分钟），CP55,940和Δ⁹-THC诱导强啡肽B的释放显著增加了两倍。AEA没有显著释放强啡肽B。在用这些药物进行30分钟预处理后，虽然CP55,940和Δ⁹-THC的镇痛作用仍然存在，但未观察到强啡肽B的显著释放。先前的研究表明，Δ⁹-THC释放强啡肽A，而AEA不释放强啡肽A。本研究证实，尽管所有三种受试药物在10分钟时均产生了显著的镇痛作用，但内源性大麻素AEA并非通过强啡肽释放诱导镇痛。因此，我们的数据表明了AEA诱导镇痛的独特机制。
