POSSIBLE ROLE OF ADENOSINE IN THE CNS EFFECTS OF ETHANOL
POSSIBLE ROLE OF ADENOSINE IN THE CNS EFFECTS OF ETHANOL
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DOI：
10.1016/0024-3205(83)90819-6
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发表时间：
1983-01-01
期刊：
影响因子：
6.1
通讯作者：
WOOLES, WR
中科院分区：
文献类型：
--
作者：
DAR, MS;MUSTAFA, SJ;WOOLES, WR
用腺苷拮抗剂茶碱和腺苷重摄取阻断剂双嘧达莫研究腺苷对急性和慢性乙醇对中枢神经系统影响的影响。用全脑粗膜研究了腺苷的结合特性。茶碱在急性给药前的预处理显著缩短了乙醇诱导的睡眠时间，同样也减少了运动不协调的强度和持续时间。在慢性乙醇处理的小鼠中，茶碱对乙醇诱导的催眠和运动不协调的影响与急性实验相似。潘生丁可明显延长乙醇催眠的持续时间，增强急性乙醇所致的运动不协调。在慢性乙醇处理的小鼠中，双嘧达莫不能增强乙醇的运动不协调效应，尽管它能够延长乙醇的催眠时间，与急性乙醇研究中的结果相似。无论是在急性还是慢性研究中，这两种药物对酒精引起的体温过低都没有任何影响。酒精摄入10天后，腺苷解离常数无明显变化，脑腺苷受体数目增加28%，但差异无统计学意义。戒断后24和48h，腺苷受体数量减少40%，72 h恢复到戒断前水平，解离常数在24和48 h降低，72 h恢复到戒断前水平。腺苷结合特性的显著变化以及药物对乙醇的某些中枢神经系统效应的影响，既影响了腺苷与其受体的结合，也影响了腺苷的可利用性，提示腺苷可能参与了乙醇的某些中枢神经系统效应的表达。
The ability of adenosine to modify the CNS effects of acute and chronic ethanol was studied by using theophylline, an adenosine antagonist, and dipyridamole, a blocker of adenosine reuptake. The binding characteristics of adenosine were studied using crude membranes of whole brain. Theophylline pretreatment prior to acute ethanol administration markedly reduced the duration of ethanol-induced sleep and similarly decreased the intensity and duration of motor incoordination. In chronic ethanol treated mice the effect of theophylline on ethanol-induced hypnosis and motor incoordination was similar to the acute experiment. Dipyridamole markedly prolonged and duration of ethanol-induced hypnosis and potentiated the motor incoordination produced by acute ethanol. In chronic ethanol treated mice dipyridamole was not able to potentiate the motor incoordinating effect of ethanol although it was able to prolong ethanol hypnosis similar to the results obtained in the acute ethanol study. Neither drug had any effect on ethanol-induced hypothermia, in either the acute or chronic studies. After 10 days of ethanol ingestion the adenosine dissociation constant was unchanged while the number of brain adenosine receptors was increased 28% although the increase did not reach statistical significance. The number of adenosine receptors was reduced 40% at 24 and 48 h after withdrawal and returned to pre-withdrawal levels at 72 h. The dissociation constant was reduced at 24 and 48 h but by 72 h had returned to prewithdrawal levels. The marked changes in adenosine binding characteristics as well as the modification of some CNS effects of ethanol by drugs which influence either adenosine binding to its receptor or the availability of adenosine suggests that adenosine may be involved in the expression of some of the CNS effects of ethanol.