Sánchez-Blázquez P, Garzón J
Neuropharmacology Unit, Cajal Institute, C.S.I.C., Madrid, Spain.
Life Sci. 1991;48(18):1721-7. doi: 10.1016/0024-3205(91)90208-s.
Cholera toxin, an agent that impairs the function of Gs transducer proteins, was injected (0.5 microgram/mouse, icv) and the antinociceptive activity of opioids and clonidine was studied 24h later in the tail-flick test. In these animals, an enhancement of the analgesic potency of morphine, beta-endorphin and clonidine could be observed. Cholera toxin did not modify the antinociception evoked by the enkephalin derivatives DAGO and DADLE. Pertussis toxin that catalyses the ADP ribosylation of alpha subunits of Gi/Go regulatory proteins was given icv (0.5 microgram/mouse). This treatment reduced the analgesic effect of opioids and clonidine. However, while the analgesia elicited by DAGO, DADLE and clonidine was greatly decreased, the effect of morphine and beta-endorphin was reduced to a moderate extent. It is concluded that Gi/Go regulatory proteins functionally coupled to opioid and alpha 2 receptors are implicated in the efficacy displayed by opioids and clonidine to produce supraspinal analgesia. Moreover, these two receptors are susceptible to regulation by a process that might involve a Gs protein.
向小鼠脑室内注射霍乱毒素（0.5微克/只），该毒素可损害Gs转导蛋白的功能。24小时后，在甩尾试验中研究阿片类药物和可乐定的抗伤害感受活性。在这些动物中，可以观察到吗啡、β-内啡肽和可乐定的镇痛效力增强。霍乱毒素并未改变脑啡肽衍生物DAGO和DADLE引起的抗伤害感受作用。向小鼠脑室内注射百日咳毒素（0.5微克/只），该毒素可催化Gi/Go调节蛋白的α亚基进行ADP核糖基化。这种处理降低了阿片类药物和可乐定的镇痛效果。然而，虽然DAGO、DADLE和可乐定引起的镇痛作用大大降低，但吗啡和β-内啡肽的作用仅中度降低。由此得出结论，与阿片类和α2受体功能偶联的Gi/Go调节蛋白与阿片类药物和可乐定产生脊髓上镇痛作用的效能有关。此外，这两种受体易受可能涉及Gs蛋白的过程的调节。
