Galeotti N, Ghelardini C, Bartolini A
Department of Preclinical and Clinical Pharmacology, University of Florence, Italy.
Eur J Pharmacol. 1996 Jul 18;308(2):125-33. doi: 10.1016/0014-2999(96)00299-3.
The effect of pretreatment with pertussis toxin at the doses of 0.25 and 0.50 micrograms per mouse i.c.v. on the analgesic effect produced by morphine (7 mg kg-1 s.c.), baclofen (4 mg kg-1 s.c.), diphenhydramine (20 mg kg-1 s.c.), clomipramine (25 mg kg-1 s.c.) and physostigmine (0.1-0.2 mg kg-1 s.c.) was investigated in the mouse hot-plate test. Seven days after a single injection of pertussis toxin, inhibition of morphine and diphenhydramine analgesia was observed, whereas 11 days after pertussis toxin pretreatment, baclofen- and clomipramine-induced antinociception was also reduced. By contrast, pertussis toxin had no effect on physostigmine-induced antinociception. The present results indicate that the activation of pertussis toxin-sensitive G-proteins represents an important transduction step in the central analgesia induced by opioids, antihistaminics, GABAB (gamma-aminobutyric acid B) agonists and tricyclic antidepressants, but not by cholinomimetics.
在小鼠热板试验中，研究了以每只小鼠脑室内注射0.25微克和0.50微克百日咳毒素进行预处理，对吗啡（7毫克/千克，皮下注射）、巴氯芬（4毫克/千克，皮下注射）、苯海拉明（20毫克/千克，皮下注射）、氯米帕明（25毫克/千克，皮下注射）和毒扁豆碱（0.1 - 0.2毫克/千克，皮下注射）产生的镇痛作用的影响。单次注射百日咳毒素7天后，观察到吗啡和苯海拉明镇痛作用受到抑制，而在百日咳毒素预处理11天后，巴氯芬和氯米帕明诱导的抗伤害感受也降低。相比之下，百日咳毒素对毒扁豆碱诱导的抗伤害感受没有影响。目前的结果表明，百日咳毒素敏感的G蛋白的激活是阿片类药物、抗组胺药、GABAB（γ-氨基丁酸B）激动剂和三环类抗抑郁药诱导的中枢镇痛中的一个重要转导步骤，但胆碱能拟似药诱导的中枢镇痛不涉及此步骤。
