Yuki T, Thurman R G
Adv Exp Med Biol. 1980;132:689-95. doi: 10.1007/978-1-4757-1419-7_71.
Gastric intubation of female Sprague-Dawley rats (80-150 g) with one large dose (5 g/kg) of ethanol nearly doubled oxygen uptake of the isolated, perfused rat liver in only 2.5 hours. This increased hepatic respiration can account for the Swift Increase in Alcohol Metabolism (SIAM). Inhibition of enhanced oxygen and ethanol uptake by KCN (2 mM) and 4-methylpyrazole (0.8 mM) indicated the involvement of the mitochondrial respiratory chain and alcohol dehydrogenase in this phenomenon, respectively. Epinephrine (2 mg/kg, i.p.) mimicked the increase in respiration observed with ethanol; however, the effects of epinephrine and ethanol were not additive. Pretreatment with alpha- and beta-adrenergic blocking agents, hypophysectomy and adrenalectomy prevented the increase in oxygen and ethanol uptake due to ethanol treatment. These data suggest that hormones including epinephrine are involved in the mechanism of SIAM. Hormone action in all likelihood activates a number of metabolic ATPase activities which lead to elevated oxygen uptake. One such process involved in the activation of oxygen uptake is diminished glycolysis, a ATP producing reaction sequence. The ADP not phosphorylated in the cytosol then enters the mitochondria where it stimulates oxygen uptake and NADH reoxidation. This ultimately leads to an acceleration of ADH-dependent ethanol metabolism.
给体重80 - 150克的雌性斯普拉格-道利大鼠进行胃插管，一次性给予大剂量（5克/千克）乙醇后，仅在2.5小时内，分离灌注的大鼠肝脏的氧摄取量就几乎增加了一倍。这种肝脏呼吸的增加可以解释酒精代谢的快速增加（SIAM）。用2毫摩尔的氰化钾（KCN）和0.8毫摩尔的4 - 甲基吡唑抑制氧摄取和乙醇摄取的增强，分别表明线粒体呼吸链和乙醇脱氢酶参与了这一现象。肾上腺素（2毫克/千克，腹腔注射）模拟了乙醇引起的呼吸增加；然而，肾上腺素和乙醇的作用并非相加的。用α - 和β - 肾上腺素能阻断剂进行预处理、垂体切除和肾上腺切除可防止因乙醇处理导致的氧摄取和乙醇摄取增加。这些数据表明，包括肾上腺素在内的激素参与了SIAM机制。激素作用很可能激活了许多代谢性ATP酶活性，从而导致氧摄取增加。参与激活氧摄取的一个这样的过程是糖酵解减少，糖酵解是一个产生ATP的反应序列。在细胞质中未磷酸化的ADP然后进入线粒体，在那里它刺激氧摄取和NADH再氧化。这最终导致依赖乙醇脱氢酶的乙醇代谢加速。
