Rabin R A, Bode D C, Molinoff P B
Biochem Pharmacol. 1986 Jul 15;35(14):2331-5. doi: 10.1016/0006-2952(86)90459-4.
The effects of butanol, ethanol, and ketamine on adenylate cyclase activity and fluorescence anisotropy were determined in membranes prepared from L6 cells. The experiments were designed to test the hypothesis that the effects of ethanol on adenylate cyclase activity are a consequence of ethanol-induced changes in bulk membrane order. Butanol and ethanol elicited concentration-dependent increases in adenylate cyclase activity and caused decreases in the fluorescence anisotropy of diphenylhexatriene. Butanol was more potent than ethanol in reducing fluorescence anisotropy, and it elicited a greater reduction in fluorescence anisotropy than did ethanol. Butanol was also more potent than ethanol in activating adenylate cyclase, but the highest concentration of butanol used caused a smaller increase in enzyme activity than did the highest concentration of ethanol. When the percent change in adenylate cyclase activity was plotted against the percent change in fluorescence anisotropy at each concentration of alcohol, the increase in isoproterenol-stimulated adenylate cyclase activity per unit change in fluorescence polarization was greater with ethanol than with butanol. Ketamine decreased fluorescence anisotropy but, unlike the alcohols, ketamine caused a decrease in adenylate cyclase activity. A reduction in assay temperature attenuated both the ethanol-induced activation of adenylate cyclase activity and the ethanol-induced reduction in fluorescence anisotropy. Although the data are consistent with the theory that ethanol acts upon a hydrophobic region of the membrane to enhance adenylate cyclase activity, activation of the enzyme does not appear to be a consequence of a decrease in bulk membrane order.
在从L6细胞制备的细胞膜中测定了丁醇、乙醇和氯胺酮对腺苷酸环化酶活性及荧光偏振的影响。这些实验旨在检验以下假设：乙醇对腺苷酸环化酶活性的影响是乙醇诱导的整体膜有序性变化的结果。丁醇和乙醇引起腺苷酸环化酶活性呈浓度依赖性增加，并导致二苯基己三烯的荧光偏振降低。在降低荧光偏振方面，丁醇比乙醇更有效，且其引起的荧光偏振降低幅度大于乙醇。在激活腺苷酸环化酶方面，丁醇也比乙醇更有效，但所用丁醇的最高浓度引起的酶活性增加幅度小于乙醇的最高浓度。当将每种酒精浓度下腺苷酸环化酶活性的百分比变化与荧光偏振的百分比变化作图时，异丙肾上腺素刺激的腺苷酸环化酶活性每单位荧光偏振变化的增加幅度，乙醇组大于丁醇组。氯胺酮降低了荧光偏振，但与醇类不同的是，氯胺酮导致腺苷酸环化酶活性降低。测定温度降低减弱了乙醇诱导的腺苷酸环化酶活性激活以及乙醇诱导的荧光偏振降低。尽管数据与乙醇作用于膜的疏水区域以增强腺苷酸环化酶活性的理论一致，但该酶的激活似乎并非整体膜有序性降低的结果。
