Whetton A D, Needham L, Margison G P, Dodd N J, Houslay M D
Biochim Biophys Acta. 1984 Jun 13;773(1):106-12. doi: 10.1016/0005-2736(84)90555-8.
The effect of the hepatocarcinogen dimethylnitrosamine on rat liver plasma membrane adenylate cyclase activity and lipid fluidity was assessed. Glucagon-stimulated adenylate cyclase activity exhibited a complex response to increasing concentrations of dimethylnitrosamine, whereas fluoride-stimulated adenylate cyclase activity was progressively inhibited. Maximal inhibitory effects were observed at a concentration of 15 mM in both cases. The activity of detergent-solubilized adenylate cyclase was unaffected by dimethylnitrosamine. ESR analysis using a fatty acid spin probe showed that dimethylnitrosamine produced a marked, dose-dependent reduction in the fluidity of the plasma membrane with a maximal effect occurring at 20 mM. Dimethylnitrosamine also elevated the temperature at which the lipid phase separation occurred in rat liver plasma membranes, from 28 degrees C to 31 degrees C. The non-carcinogenic but structurally similar compound, dimethylamine hydrochloride neither inhibited adenylate cyclase nor decreased plasma membrane fluidity. It is suggested that the decrease in membrane fluidity, induced by dimethylnitrosamine, via its effects on membrane fluidity, could influence plasma membrane function and cellular regulation.
评估了肝癌致癌物二甲基亚硝胺对大鼠肝质膜腺苷酸环化酶活性和脂质流动性的影响。胰高血糖素刺激的腺苷酸环化酶活性对二甲基亚硝胺浓度升高呈现出复杂的反应，而氟化物刺激的腺苷酸环化酶活性则逐渐受到抑制。在两种情况下，均在15 mM浓度时观察到最大抑制作用。去污剂增溶的腺苷酸环化酶活性不受二甲基亚硝胺影响。使用脂肪酸自旋探针的电子自旋共振分析表明，二甲基亚硝胺使质膜流动性显著降低，呈剂量依赖性，最大效应出现在20 mM时。二甲基亚硝胺还使大鼠肝质膜脂质相分离发生的温度从28℃升高到31℃。非致癌但结构相似的化合物盐酸二甲胺既不抑制腺苷酸环化酶，也不降低质膜流动性。提示二甲基亚硝胺通过其对膜流动性的影响而导致的膜流动性降低，可能会影响质膜功能和细胞调节。
