Gandhi V C, Ross D H
Alcohol. 1987 Jan-Feb;4(1):25-30. doi: 10.1016/0741-8329(87)90056-5.
The effects of alpha 1- and alpha 2-adrenergic agonists, viz., phenylephrine and clonidine, respectively, were studied on rat liver plasma membrane Ca++-ATPase. Phenylephrine produced a 23% inhibition of enzyme activity at 5 microM. Prazosin, an alpha 1 antagonist, completely prevented the effect of phenylephrine. Clonidine produced a comparable inhibition of Ca++-ATPase, but was not reversed by the antagonist yohimbine, suggesting a lack of functionally significant alpha 2 receptors as previously reported. The results support the role of high-affinity Ca++-ATPase in liver plasma membranes in the control of cytosolic free Ca++ levels through regulation by alpha 1-adrenergic receptors. In vitro and acute ethanol exposure produced inhibition of plasma membrane Ca++-ATPase. In addition, ethanol treatment significantly reversed the inhibitory effect of phenylephrine on Ca++-ATPase. Chronic ethanol exposure for four weeks increased Ca++-ATPase activity over control and increased enzyme activity in the presence of phenylephrine. These results demonstrate that ethanol alters the alpha-adrenergic receptor interaction with Ca++-ATPase resulting in reduced receptor regulation of cytosolic Ca++ levels. These changes may prevent the liver from maintaining Ca++ levels for second messenger functions, such as glycolysis and gluconeogenesis.
分别研究了α1 - 和α2 - 肾上腺素能激动剂（即去氧肾上腺素和可乐定）对大鼠肝质膜Ca++ - ATP酶的作用。去氧肾上腺素在5微摩尔浓度时使酶活性受到23%的抑制。α1拮抗剂哌唑嗪完全阻断了去氧肾上腺素的作用。可乐定对Ca++ - ATP酶产生了类似的抑制作用，但拮抗剂育亨宾不能使其逆转，这表明如先前报道的那样，缺乏功能上重要的α2受体。这些结果支持了肝质膜中高亲和力Ca++ - ATP酶通过α1 - 肾上腺素能受体调节在控制胞质游离Ca++水平中的作用。体外和急性乙醇暴露均抑制质膜Ca++ - ATP酶。此外，乙醇处理显著逆转了去氧肾上腺素对Ca++ - ATP酶的抑制作用。四周的慢性乙醇暴露使Ca++ - ATP酶活性高于对照组，并在有去氧肾上腺素存在时增加了酶活性。这些结果表明，乙醇改变了α - 肾上腺素能受体与Ca++ - ATP酶的相互作用，导致对胞质Ca++水平的受体调节减少。这些变化可能会阻止肝脏维持Ca++水平以进行第二信使功能，如糖酵解和糖异生。
