Gonzales R A, Leslie S W
Biochem Pharmacol. 1985 May 15;34(10):1619-25. doi: 10.1016/0006-2952(85)90625-2.
The effects of barbiturates on adenosine movements across the synaptic plasma membrane have been investigated using rodent whole brain synaptosomes. The hypothesis tested was that some of the depressant actions of these drugs may be mediated through interference with an endogenous adenosine system. Adenosine uptake was studied using synaptosomes prepared from Swiss-Webster mice. After preincubation at 37 degrees, [3H]adenosine was added to the synaptosomes in the presence or absence of pentobarbital, methohexital, phenobarbital, or 5-(2-cyclohexylideneethyl)-5-ethyl barbituric acid (CHEB) at various concentrations and times. All four compounds significantly inhibited [3H]adenosine uptake at concentrations of 100-300 microM. Pentobarbital did not affect the distribution of synaptosomal adenosine metabolites. Release of [3H]adenosine was studied using the P2 pellet from male CD-1 mice. Addition of 50 mM KCl caused an enhancement of 3H-efflux mainly due to increased release of adenosine and inosine. This effect was abolished in the presence of 250 microM ethylene glycol bis(beta-aminoethyl-ether)-N,N2-tetraacetic acid (EGTA). Pentobarbital, 0.3 mM, caused a significant increase in the net potassium-induced release of [3H]adenosine. These results suggest that some of the depressant effects of barbiturates may be due to inhibition of adenosine reuptake and enhancement of release resulting in elevated synaptic adenosine levels.
已使用啮齿动物全脑突触体研究了巴比妥类药物对腺苷跨突触质膜转运的影响。所检验的假设是，这些药物的某些抑制作用可能是通过干扰内源性腺苷系统介导的。使用从瑞士-韦伯斯特小鼠制备的突触体研究腺苷摄取。在37℃预孵育后，在存在或不存在不同浓度和时间的戊巴比妥、美索比妥、苯巴比妥或5-(2-环己叉乙基)-5-乙基巴比妥酸(CHEB)的情况下，将[3H]腺苷添加到突触体中。所有四种化合物在100-300微摩尔浓度下均显著抑制[3H]腺苷摄取。戊巴比妥不影响突触体腺苷代谢物的分布。使用雄性CD-1小鼠的P2沉淀研究[3H]腺苷的释放。添加50 mM氯化钾导致3H外流增加，主要是由于腺苷和肌苷释放增加。在存在250微摩尔乙二醇双(β-氨基乙基醚)-N,N'-四乙酸(EGTA)的情况下，这种作用被消除。0.3 mM的戊巴比妥导致钾诱导的[3H]腺苷净释放显著增加。这些结果表明，巴比妥类药物的某些抑制作用可能是由于抑制腺苷再摄取和增强释放，导致突触腺苷水平升高。
