Carmichael F J, Orrego H, Israel Y
Department of Pharmacology, University of Toronto, Ontario, Canada.
Alcohol Alcohol Suppl. 1993;2:411-8.
Ethanol administration leads to a marked increase in hepatic blood flow, resulting from an increase in mesenteric blood flow. Studies presented indicate that the increase in portal blood flow induced by ethanol is mediated by acetate. Acetate infusion at rates which achieve blood concentrations equal to those following ethanol administration, fully reproduce this effect of ethanol. The adenosine receptor blocker 8-phenyltheophilline (8PT) fully abolishes the increase in portal blood flow induced by both ethanol and acetate. We have proposed that the extrahepatic metabolism of acetate into acetyl-CoA yields AMP and adenosine. Studies also indicate that adenosine receptor activation has a major contribution to the CNS depressant effects of ethanol at low concentrations of ethanol (below 1.5 g/kg) where the production of acetate is near maximal and the physico-chemical effects of ethanol are minor. Acetate significantly potentiates the CNS depressant effects of general anesthetics. Data to be presented indicate that for some behaviours, acetate through an adenosine-receptor activation potentiates the effects of ethanol while in other behavioural tests they antagonize ethanol effects.
给予乙醇会导致肝血流量显著增加，这是由肠系膜血流量增加所致。所展示的研究表明，乙醇诱导的门静脉血流量增加是由乙酸盐介导的。以能达到与给予乙醇后相同血药浓度的速率输注乙酸盐，可完全重现乙醇的这一作用。腺苷受体阻断剂8-苯基茶碱（8PT）可完全消除乙醇和乙酸盐诱导的门静脉血流量增加。我们曾提出，乙酸盐在肝外代谢为乙酰辅酶A会产生AMP和腺苷。研究还表明，在低浓度乙醇（低于1.5 g/kg）时，腺苷受体激活对乙醇的中枢神经系统抑制作用有主要贡献，此时乙酸盐的生成接近最大值，而乙醇的物理化学作用较小。乙酸盐可显著增强全身麻醉药的中枢神经系统抑制作用。即将展示的数据表明，对于某些行为，乙酸盐通过激活腺苷受体增强乙醇的作用，而在其他行为测试中，它们则拮抗乙醇的作用。
