Lutfy K, Chang S C, Candido J, Jang Y, Sierra V, Yoburn B C
College of Pharmacy and Allied Health Professions, St. John's University, Queens, NY 11439.
Brain Res. 1991 Mar 29;544(2):191-5. doi: 10.1016/0006-8993(91)90053-x.
The present study evaluates the effect of pertussis toxin (PTX) on morphine-induced analgesia and lethality. Mice were injected with 0.2 microgram PTX intracerebroventricularly (i.c.v.) and 0.2 micrograms PTX intrathecally (i.t.) or saline. Mice were tested for morphine-induced analgesia (tail flick) and lethality 16 days later; mice were also examined for pentobarbital-induced mortality. Morphine analgesic potency was decreased by approximately 4-fold in PTX-treated mice compared to controls. Conversely, the lethal potency of morphine was increased by 10-fold in PTX-treated mice compared to controls. PTX treatment did not alter the lethal potency of pentobarbital. Morphine-induced analgesia and lethality were dose-dependently antagonized by naloxone in both PTX and saline-treated groups. The results of this study suggest that morphine analgesia is mediated through PTX-sensitive G proteins. On the other hand, morphine-induced lethality appears to be limited by PTX-sensitive factor(s) since PTX treatment enhanced morphine's lethal potency. The increase in lethal potency of morphine may be due to unmasking of an excitatory opioid receptor mediated effect by PTX.
本研究评估了百日咳毒素（PTX）对吗啡诱导的镇痛作用和致死性的影响。给小鼠脑室内注射（i.c.v.）0.2微克PTX、鞘内注射（i.t.）0.2微克PTX或生理盐水。16天后检测小鼠吗啡诱导的镇痛作用（甩尾试验）和致死性；同时检测小鼠戊巴比妥诱导的死亡率。与对照组相比，PTX处理组小鼠吗啡的镇痛效力降低了约4倍。相反，与对照组相比，PTX处理组小鼠吗啡的致死效力增加了10倍。PTX处理未改变戊巴比妥的致死效力。在PTX处理组和生理盐水处理组中，纳洛酮均剂量依赖性地拮抗吗啡诱导的镇痛作用和致死性。本研究结果表明，吗啡镇痛作用是通过对PTX敏感的G蛋白介导的。另一方面，由于PTX处理增强了吗啡的致死效力，吗啡诱导的致死性似乎受到对PTX敏感的因子的限制。吗啡致死效力的增加可能是由于PTX暴露了兴奋性阿片受体介导的效应。
