Cullen N, Carlen P L
Department of Physiology, University of Toronto, Ont. Canada.
Brain Res. 1992 Aug 14;588(1):49-57. doi: 10.1016/0006-8993(92)91343-d.
Acetate is the primary breakdown product of ethanol metabolism in the liver and has been found in the brain following ethanol ingestion in rats. Systemically administered acetate has been shown to cause motor impairment, an effect which is blocked by the adenosine receptor blocker, 8-phenyltheophylline (8-PT). The effects of sodium acetate were investigated in this study using intracellular recording techniques in rat hippocampal dentate granule cells, and were compared to the actions of ethanol and adenosine individually and in conjunction with 8-PT. Acetate hyperpolarized the membrane at 0.4-0.8 mM. The amplitude and duration of the postspike train afterhyperpolarization (AHP) were increased by acetate when the cell was repolarized to the control resting membrane potential. Comparable results were seen in voltage clamp. Acetate also decreased spike frequency adaptation. The effects of acetate were mimicked by adenosine (50 microM) and ethanol (20 mM). The ethanol effects occluded those produced by acetate. All of the effects of acetate, adenosine and ethanol could be inhibited with prior perfusion of 8-PT (1-10 microM). These data suggest that the actions of the major metabolite of ethanol, acetate, may be mediated by adenosine receptor activation.
乙酸盐是肝脏中乙醇代谢的主要分解产物，在给大鼠摄入乙醇后已在其大脑中发现。全身给予乙酸盐已被证明会导致运动障碍，腺苷受体阻滞剂8-苯基茶碱（8-PT）可阻断这一效应。本研究使用细胞内记录技术在大鼠海马齿状颗粒细胞中研究了乙酸钠的作用，并将其与乙醇和腺苷单独以及与8-PT联合使用时的作用进行了比较。乙酸盐在0.4-0.8 mM时使膜超极化。当细胞复极化至对照静息膜电位时，乙酸盐增加了锋电位串后超极化（AHP）的幅度和持续时间。在电压钳实验中也观察到了类似结果。乙酸盐还降低了锋电位频率适应性。腺苷（50 μM）和乙醇（20 mM）模拟了乙酸盐的作用。乙醇的作用掩盖了乙酸盐产生的作用。预先灌注8-PT（1-10 μM）可抑制乙酸盐、腺苷和乙醇的所有作用。这些数据表明，乙醇的主要代谢产物乙酸盐的作用可能是由腺苷受体激活介导的。
