EFFECT OF ACUTE ETHANOL ON UPTAKE OF [H-3] ADENOSINE BY RAT CEREBELLAR SYNAPTOSOMES
EFFECT OF ACUTE ETHANOL ON UPTAKE OF [H-3] ADENOSINE BY RAT CEREBELLAR SYNAPTOSOMES
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DOI：
10.1111/j.1530-0277.1989.tb00338.x
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发表时间：
1989-06-01
期刊：
影响因子：
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通讯作者：
DAR, MS
中科院分区：
文献类型：
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作者：
CLARK, M;DAR, MS
许多类CNS作用药物已被认为至少部分通过抑制腺苷摄取起作用。在已知参与协调和调节正常运动活动的大鼠脑区（小脑）中研究了[3 H]腺苷的突触体摄取和急性乙醇对其的影响。发现[3 H]腺苷的摄取与时间（约40秒）和增加的腺苷浓度（高达1.5 μ M）成线性关系。[3 H]腺苷的摄取被地拉卓抑制（IC 50 = 2.5 × 10 - 6）。10-7 M）以剂量依赖性方式。药理学和/或毒理学相关浓度的乙醇（2.5至100 mM）显著抑制12%至15%的[3 H]腺苷摄取。Lineweaver-Burk图表明体外（25 mM）和体内（1.5 g/kg i. p.; 30 mM血液水平）乙醇降低腺苷摄取的Km以及Vmax值至几乎相同的程度。在体内乙醇的情况下，在测定期间不存在乙醇，因为突触体制备将洗掉残留的乙醇。本研究的结果表明，在体内乙醇可能的膜改变。结果表明，体外致醉浓度乙醇和体内急性乙醇（1.5g/kg）均能抑制[3 H]腺苷的摄取。这可能部分解释了内源性腺苷在乙醇诱导的运动障碍中的调节作用。
Many classes of CNS-acting drugs have been suggested to act at least partially via inhibition of adenosine uptake. Synaptosomal uptake of [3H]adenosine and the effect of acute ethanol on it were studied in a rat brain area known to be involved in the coordination and modulation of normal motor activity, the cerebellum. Uptake of [3H]adenosine was found to be linear with time (about 40 sec) and increasing concentrations (up to 1.5 .mu.M) of adenosine. The uptake of [3H]adenosine was inhibited by dilazep (IC50 = 2.5 .times. 10-7 M) in a dose-dependent manner. Pharmacologically and/or toxicologically relevant concentrations of ethanol (2.5 to 100 mM) significantly inhibited the uptake of [3H]adenosine between 12 and 15%. Lineweaver-Burk plots indicated that both in vitro (25 mM) and in vivo (1.5 g/kg i.p.; 30 mM blood level) ethanol lowered Km as well as Vmax values for adenosine uptake to nearly the same extent. In the case of in vivo ethanol, no ethanol was present during the assay since synaptosome preparation would wash out residual ethanol. The results of the present study indicate possible membranal alterations by in vivo ethanol. It is concluded that the uptake of [3H]adenosine is inhibited by intoxicating concentration of ethanol in vitro and by acute ethanol (1.5 g/kg) in vivo. This may partially explain the modulatory role of endogenous adenosine in ethanol-induced motor disturbances.