Ishikawa Y, Ciosek C P, Fahey J V, Newcombe D S
J Cyclic Nucleotide Res. 1976;2(2):115-28.
Prostaglandin (PG) synthetase activity and selective hormone responsiveness were examined in normal and SV40 transformed WI-38 fibroblasts (VA13-2RA). The transformed VA13-2RA cells have significantly reduced rates of PGE1, PGE2, PGF1alpha and PGF2alpha synthesis as compared to the normal WI-38 fibroblast. The transformed cell in contrast to the normal cell hyperresponds to stimulation by L-epinephrine (10 muM) and PGE1 (8.5 muM) but is unresponsive to bradykinin (BK) as measured by the accumulation of intracellular cyclic AMP. Indomethacin treatment does not significantly alter the PGE1 and L-epinephrine (EPI) responsiveness of the normal WI-38 fibroblast, however it abolishes the BK response in these cells. These results provide further evidence for the dependency of cell activation by bradykinin on the PG synthetase system. No experimental data was found to support the role of PGs as negative regulators of PGE1 and EPI responsiveness in the WI-38 fibroblast. Using the VA13-2RA cells, limited attempts to recover PG synthetase activity comparable to that found in normal WI-38 cells were unsuccessful. The VA13-2RA cell and its normal counterpart represent models for investigating the role of PGs in cell function and the mechanism of BK activation and its effect on cell metabolism.
在正常和经SV40转化的WI-38成纤维细胞（VA13-2RA）中检测了前列腺素（PG）合成酶活性和选择性激素反应性。与正常的WI-38成纤维细胞相比，转化后的VA13-2RA细胞中PGE1、PGE2、PGF1α和PGF2α的合成速率显著降低。与正常细胞相比，转化细胞对L-肾上腺素（10 μM）和PGE1（8.5 μM）的刺激反应过度，但通过细胞内环磷酸腺苷的积累测量，其对缓激肽（BK）无反应。吲哚美辛处理不会显著改变正常WI-38成纤维细胞对PGE1和L-肾上腺素（EPI）的反应性，然而它消除了这些细胞中的BK反应。这些结果为缓激肽激活细胞对PG合成酶系统的依赖性提供了进一步的证据。未发现实验数据支持PG作为WI-38成纤维细胞中PGE1和EPI反应性负调节因子的作用。使用VA13-2RA细胞，恢复与正常WI-38细胞相当的PG合成酶活性的有限尝试未成功。VA13-2RA细胞及其正常对应物代表了研究PG在细胞功能中的作用以及BK激活机制及其对细胞代谢影响的模型。
