Gruol D J, Dalton D K
J Cell Physiol. 1984 Apr;119(1):107-18. doi: 10.1002/jcp.1041190118.
Cyclic AMP and glucocorticoid hormones each promote a cytolytic response in the murine lymphoid cell line WEHI-7.1 (W7). The sensitivity to dibutyryl cyclic AMP (dbcAMP), but not dexamethasone, can be enhanced by several psychotropic drugs that have the capacity to interfere with a variety of calcium-regulated functions. We have characterized the response of W7 cells to the phenothiazine trifluoperazine (TFP) and found that TFP concentrations, which decreased the growth rate by twofold, shifted the dose response to dbcAMP approximately tenfold. A similar but smaller shift was seen with the phosphodiesterase inhibitor methylisobutylxanthine (MIX). The effects of TFP and MIX on the dbcAMP response were additive, suggesting that TFP may act to increase the sensitivity of W7 cells to the action of cAMP-dependent protein kinase, and that the increased sensitivity may be due to altered lytic functions coregulated by both cAMP and calcium. The change in the dose response to dbcAMP caused by TFP provided a means of selection to obtain variants that were altered in their capacity to respond to dbcAMP, TFP, or the combination of the two drugs. Eight (out of 36) of the lines that were obtained after a mutagenesis and combined drug selection have been partially characterized. This has revealed the existence of several new phenotypes. Most have an altered response to dbcAMP in the presence of TFP and are likely to represent variants that have not been observed before.
环磷腺苷（cAMP）和糖皮质激素各自都能促进小鼠淋巴细胞系WEHI-7.1（W7）的溶细胞反应。几种具有干扰多种钙调节功能能力的精神药物可增强对二丁酰环磷腺苷（dbcAMP）的敏感性，但对地塞米松则无此作用。我们已对W7细胞对吩噻嗪三氟拉嗪（TFP）的反应进行了表征，发现TFP浓度使生长速率降低两倍，使对dbcAMP的剂量反应曲线大约右移了10倍。磷酸二酯酶抑制剂甲基异丁基黄嘌呤（MIX）也观察到类似但较小的右移。TFP和MIX对dbcAMP反应的影响是相加的，这表明TFP可能通过增加W7细胞对cAMP依赖性蛋白激酶作用的敏感性来发挥作用，而这种增加的敏感性可能是由于cAMP和钙共同调节的裂解功能发生了改变。TFP引起的对dbcAMP剂量反应的变化提供了一种选择方法，以获得对dbcAMP、TFP或这两种药物组合反应能力改变的变体。在诱变和联合药物选择后获得的36个细胞系中有8个已得到部分表征。这揭示了几种新表型的存在。大多数在TFP存在下对dbcAMP的反应发生了改变，很可能代表以前未观察到的变体。
