Hickie R A, Jan S H, Datta A
Cancer Res. 1975 Mar;35(3):596-600.
Homogenate and plasma membrane fractions of Morris hepatoma 5123tc (h) and rat liver were studied with regard to their relative basal activties of adenylate cyclase and to the comparative responsiveness of this enzyme to glucagon, sodium fluoride, epinephrine, prostaglandin E1, and insulin. The basal adenylate cyclase activities of the hepatoma fractions were found to be similar to those of liver at an adenosine 5'triphosphate concentration of 3.2 mM; if the substrate affinity (Km adenosine 5'-triphosphate) of the tumor enzyme is comparable to that of liver, these findings suggest that the reduced basal cyclic adenosine 3':5'-monophosphate levels found to occur in hepatoma 5123tc (h) probably are not due to a decreased basal rate of formation of this cyclic nucleotide. Glucagon (5.6 muM) significantly stimulated adenylate cyclase in both fractions of hepatoma and livers; however, the responsiveness of the tumor enzyme to this hormone was substantially lower than the responsiveness of liver for both homogenate and plasma membrane preparations; i.e., activities were enhanced 18-fold (relative to the basal activity)for liver homogenate compared with only a 6-fold increase for tumor. With the plasma membrane preparations, glucagon increased the activities 5- and 3.5-fold in liver and hepatoma, respectively. Sodium fluoride (10mM), in contrast to glucagon, increased the adenylate cyclase activity to approximately the same extent (about 10-fold) in the liver and hepatoma preparations. Epinephrine (100 muM) enhanced the liver and hepatoma homogenate activites 3- to 4-fold and the hepatoma plasma membrane activities 2-fold; however, the liver plasma membrane activites were not increased. Prostaglandin E1 (56.6 MUM) significantly increased adenylate cyclase activites of liver and hepatoma homogenates (i.e., 1.5- and 3-fold, respectively) but not of the plasma membrane preparations. Insulin (0.7 muM) did not significantly alter adenylate cyclase activities in any of the preparations.
对莫里斯肝癌5123tc（h）和大鼠肝脏的匀浆及质膜部分进行了研究，涉及它们腺苷酸环化酶的相对基础活性以及该酶对胰高血糖素、氟化钠、肾上腺素、前列腺素E1和胰岛素的比较反应性。发现在腺苷5'-三磷酸浓度为3.2 mM时，肝癌部分的基础腺苷酸环化酶活性与肝脏的相似；如果肿瘤酶的底物亲和力（腺苷5'-三磷酸的Km）与肝脏的相当，这些发现表明，在肝癌5123tc（h）中发现的基础环腺苷3':5'-单磷酸水平降低可能并非由于该环核苷酸基础形成速率降低。胰高血糖素（5.6 μM）显著刺激了肝癌和肝脏两部分的腺苷酸环化酶；然而，肿瘤酶对这种激素的反应性明显低于肝脏，无论是匀浆还是质膜制剂；即，肝脏匀浆的活性相对于基础活性提高了18倍，而肿瘤仅增加了6倍。对于质膜制剂，胰高血糖素使肝脏和肝癌的活性分别提高了5倍和3.5倍。与胰高血糖素相反，氟化钠（10 mM）在肝脏和肝癌制剂中使腺苷酸环化酶活性增加到大致相同的程度（约10倍）。肾上腺素（100 μM）使肝脏和肝癌匀浆的活性提高了3至4倍，使肝癌质膜活性提高了2倍；然而，肝脏质膜活性未增加。前列腺素E1（56.6 μM）显著增加了肝脏和肝癌匀浆的腺苷酸环化酶活性（分别为1.5倍和3倍），但对质膜制剂没有影响。胰岛素（0.7 μM）在任何制剂中均未显著改变腺苷酸环化酶活性。
