Natsuki R
Faculty of Pharmaceutical Sciences, Setsunan University.
Arukoru Kenkyuto Yakubutsu Ison. 1992 Feb;27(1):57-70.
Calcium (25 mM)-stimulated incorporation of choline into phosphatidylcholine (PC) and 3H-morphine (3H-M) binding was studied using cerebral crude synaptosomal fractions from acute morphine-treated (naive), morphine-dependent and morphine-withdrawn mice. Mice became physically dependent on morphine after ingesting morphine-mixed food. Morphine dependence inhibited the incorporation of 14C-choline into PC. The injection of naloxone (1 mg/kg) to morphine-dependent mice also inhibited the incorporation of 14C-choline into PC. The injection of morphine (10 mg/kg) to morphine-withdrawn mice stimulated the incorporation of 14C-choline into PC, but had no effect, either on acute morphine-treated mice or on morphine-dependent mice. Naloxone (1 mg/kg), morphine (10 mg/kg), morphine dependence and opiate withdrawal (20 hrs after the last exposure to morphine in food) all caused about a 25% decrease in 3H-M (10(-7) M) binding to mouse brain synaptosomes. The injection of 10 mg/kg of morphine 45 min before death caused an additional 20% decrease in 3H-morphine binding in the dependent and withdrawn mice, but not in the naive mice. Stereospecific binding (SSB) of 3H-M was evaluated with respect to: 1) the effect of naloxone treatment in vivo on 3H-M binding in vitro, 2) the effect of morphine treatment in vivo on 3H-M binding in vitro; and 3) the differences between 3H-M bound (in vitro) and both naloxone and morphine treatment (in vivo). SSB activity was high in morphine-withdrawn mice. These differences may be caused by changes in the opiate receptors related to tolerance and withdrawal, and may entail between PC and membrane receptors.
使用来自急性吗啡处理(未成瘾)、吗啡依赖和吗啡戒断小鼠的脑粗突触体组分,研究了钙(25 mM)刺激的胆碱掺入磷脂酰胆碱(PC)以及3H-吗啡(3H-M)结合情况。小鼠在摄入含吗啡的食物后会对吗啡产生身体依赖性。吗啡依赖抑制了14C-胆碱掺入PC。向吗啡依赖小鼠注射纳洛酮(1 mg/kg)也抑制了14C-胆碱掺入PC。向吗啡戒断小鼠注射吗啡(10 mg/kg)刺激了14C-胆碱掺入PC,但对急性吗啡处理小鼠或吗啡依赖小鼠均无影响。纳洛酮(1 mg/kg)、吗啡(10 mg/kg)、吗啡依赖和阿片戒断(最后一次在食物中接触吗啡后20小时)均导致3H-M(10(-7) M)与小鼠脑突触体的结合减少约25%。在死亡前45分钟注射10 mg/kg吗啡,导致依赖和戒断小鼠的3H-吗啡结合额外减少20%,但对未成瘾小鼠无此影响。评估了3H-M的立体特异性结合(SSB):1)体内纳洛酮处理对体外3H-M结合的影响;2)体内吗啡处理对体外3H-M结合的影响;3)体外结合的3H-M与体内纳洛酮和吗啡处理之间的差异。吗啡戒断小鼠的SSB活性较高。这些差异可能是由与耐受性和戒断相关的阿片受体变化引起的,可能涉及PC与膜受体之间的关系。