Kitagawa T, Amano F, Akamatsu Y
Department of Chemistry, National Institute of Health, Tokyo, Japan.
Biochim Biophys Acta. 1988 Jun 22;941(2):257-63. doi: 10.1016/0005-2736(88)90186-1.
External ATP causes a marked increase in the passive permeability to phosphorylated metabolites in several types of transformed cells in alkaline medium containing low concentrations of Ca2+, but not in untransformed cells. Such increased membrane permeability with external ATP was also observed in B16 melanoma cells at pH 7.4-7.5 in both Tris-buffered saline and a growth medium containing 10% calf serum and divalent ions at normal concentrations, although a higher concentration of ATP was required. The permeability change in the growth medium was significantly enhanced by calmodulin-interacting drugs, such as trifluoperazine (TFP), N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W7) and chlorpromazine (CPZ). As expected, prolonged exposure of the cells to ATP in the serum-containing medium led to cell lysis. This ATP-dependent cell lysis was observed only in several transformed cell lines, and not in untransformed mouse fibroblasts. These results indicate that the effect of ATP on the membrane permeability in transformed cells is elicited under the physiological conditions and this would be useful in some limited way for cancer chemotherapy management.
在含有低浓度Ca2+的碱性培养基中,外源性ATP可使几种类型的转化细胞对磷酸化代谢产物的被动通透性显著增加,但对未转化细胞则无此作用。在pH 7.4 - 7.5的Tris缓冲盐溶液以及含有10%小牛血清和正常浓度二价离子的生长培养基中,B16黑色素瘤细胞也观察到外源性ATP引起的膜通透性增加,尽管所需的ATP浓度更高。钙调蛋白相互作用药物,如三氟拉嗪(TFP)、N-(6-氨基己基)-5-氯-1-萘磺酰胺(W7)和氯丙嗪(CPZ),可显著增强生长培养基中的通透性变化。正如预期的那样,细胞在含血清培养基中长时间暴露于ATP会导致细胞裂解。这种ATP依赖性细胞裂解仅在几种转化细胞系中观察到,而在未转化的小鼠成纤维细胞中未观察到。这些结果表明,ATP对转化细胞的膜通透性的影响是在生理条件下引发的,这在癌症化疗管理的某些有限方面可能会有用。