Parolaro D, Patrini G, Massi P, Parenti M, Rubino T, Giagnoni G, Gori E
Institute of Pharmacology, Faculty of Sciences, University of Milan, Italy.
Eur J Pharmacol. 1990 Feb 20;177(1-2):75-80. doi: 10.1016/0014-2999(90)90551-g.
To find whether the antipropulsive effect of morphine administered intracerebroventricularly (i.c.v.) depends on a G-protein-mediated mechanism, we studied the effect of i.c.v. pertussis toxin (PTX) pretreatment on morphine-induced inhibition of intestinal motility. The influence of PTX was evaluated on intestinal transit (charcoal meal test) and by monitoring of intestinal myoelectrical activity. The antitransit effect of morphine (10 micrograms/rat) was antagonized by about 70% 3, 6, 9 and 12 days after PTX pretreatment (1 microgram/rat) and it was partially restored after 25 days. I.c.v. morphine abolished the regular appearance of the myoelectric migrating complex (MMC) recorded in the rat jejunum and this effect was completely antagonized by PTX pretreatment. When morphine was injected 25 days after PTX, it significantly reduced MMC frequency, confirming the partial recovery seen in the transit experiments. The pertussis toxin-catalyzed ADP ribosylation of a 39-41 kDa substrate in membranes prepared from hypothalamus and midbrain of rats injected with toxin 6 days before was strongly reduced as compared to the controls. On the contrary, after 25 days, ADP ribosylation was the same in treated and control rats. Thus the antipropulsive effect of central morphine could be initiated at receptor sites which interact with G-protein substrates of pertussis toxin.
为了探究脑室内注射吗啡的抗推进作用是否依赖于G蛋白介导的机制，我们研究了脑室内注射百日咳毒素（PTX）预处理对吗啡诱导的肠动力抑制的影响。通过肠转运（炭末试验）以及监测肠肌电活动来评估PTX的影响。PTX预处理（1微克/大鼠）后3、6、9和12天，吗啡（10微克/大鼠）的抗转运作用被拮抗约70%，25天后部分恢复。脑室内注射吗啡消除了大鼠空肠中记录到的肌电移行复合波（MMC）的正常出现，而这种作用被PTX预处理完全拮抗。当在PTX注射25天后注射吗啡时，它显著降低了MMC频率，证实了在转运实验中观察到的部分恢复。与对照组相比，在注射毒素6天前的大鼠下丘脑和中脑制备的膜中，百日咳毒素催化的39 - 41 kDa底物的ADP核糖基化作用显著降低。相反，25天后，处理组和对照组大鼠的ADP核糖基化作用相同。因此，中枢性吗啡的抗推进作用可能起始于与百日咳毒素的G蛋白底物相互作用的受体位点。
