Rönnbäck L, Hansson E
Biochem Pharmacol. 1986 Nov 1;35(21):3685-92. doi: 10.1016/0006-2952(86)90652-0.
Rats were intoxicated with morphine as intraperitoneal (i.p.) single doses, or for 4 days (final dose 130 mg/kg b.w.) or for 13 days (final dose 340 mg/kg b.w.) using an ingestion method where intoxicated and control rats received the same amount of calories and fluid. The intoxicated groups showed different degrees of physical dependence, demonstrated by variously expressed abstinence symptoms after withdrawal of the drug or after administration of the opiate receptor antagonist naloxone. Soluble protein synthesis was measured in vivo in brain stem by double labelling with 3H and 14C valine and followed over time in the various rat groups after i.p. morphine injection in different doses. Protein synthesis in astroglial-enriched primary cultures from brain stem and secretion of labelled protein to the serum free incubation medium was also evaluated after morphine treatment. There were dose- and time-dependent effects of morphine on brain stem protein synthesis with an initial decrease and a later increase, 1-3 hr after a single dose of morphine administration. Following a morphine single dose of 25 mg/kg b.w. the stimulation was more rapid in onset and more pronounced in rats with a higher degree of physical dependence. Specific protein fractions including one with a subunit M.W. of approx. 80,000 were identified by electrophoretic separation of labelled proteins. Some similar protein fractions increased in synthesis and were released to the serum-free incubation medium when separating astroglial primary culture proteins after morphine treatment. It might be that the biphasic changes in protein synthesis after morphine administration underlie adaptive phenomena such as tolerance/physical dependence development and that some of the identified proteins including proteins synthesized in astroglial cells and secreted to the incubation media participate in these processes.
大鼠通过腹腔注射单剂量吗啡、或采用摄食法连续4天（最终剂量130 mg/kg体重）或连续13天（最终剂量340 mg/kg体重）进行吗啡中毒，中毒组和对照组大鼠摄入相同热量和液体。中毒组表现出不同程度的身体依赖性，通过停药后或注射阿片受体拮抗剂纳洛酮后出现的不同程度戒断症状得以证明。通过用3H和14C缬氨酸进行双重标记在体内测量脑干中的可溶性蛋白质合成，并在腹腔注射不同剂量吗啡后对不同大鼠组随时间进行跟踪。吗啡处理后还评估了脑干富含星形胶质细胞的原代培养物中的蛋白质合成以及标记蛋白质向无血清孵育培养基中的分泌情况。吗啡对脑干蛋白质合成有剂量和时间依赖性影响，单次注射吗啡后1 - 3小时，先是下降，随后上升。单次注射25 mg/kg体重的吗啡后，刺激起效更快，在身体依赖性较高的大鼠中更明显。通过对标记蛋白质进行电泳分离鉴定出特定蛋白质组分，包括一种亚基分子量约为80,000的组分。吗啡处理后分离星形胶质细胞原代培养物蛋白质时，一些类似的蛋白质组分合成增加并释放到无血清孵育培养基中。可能是吗啡给药后蛋白质合成的双相变化是耐受性/身体依赖性发展等适应性现象的基础，并且一些已鉴定的蛋白质，包括在星形胶质细胞中合成并分泌到孵育培养基中的蛋白质，参与了这些过程。
