Nagasawa K, Tsumura A, Kitazawa F, Nomiyama M, Ohnishi N, Yokoyama T
Department of Hospital Pharmacy, Kyoto Pharmaceutical University, Japan.
Biol Pharm Bull. 1995 Feb;18(2):368-71. doi: 10.1248/bpb.18.368.
We previously revealed that pirarubicin (THP) was actively taken up by rat polymorphonuclear leukocytes via a carrier-mediated transport system. In the experiment on the effects of the metabolic inhibitors, rotenone, 2,4-dinitrophenol and sodium cyanide significantly decreased the THP transport. However, sodium fluoride (NaF) significantly increased the uptake, and this result is different from that in some reports. Therefore, we examined the action of NaF on THP uptake by the leukocytes to clarify the discrepancy in the effect of NaF on drug transport. The accelerating effect of 30 mM NaF on the THP uptake by the cells had an optimum period of action (15-20 min), and was concentration-dependent (5-30 mM). Thirty mM potassium fluoride, as well as NaF, increased the uptake amount. On the other hand, NaF (5-30 mM) dose-dependently decreased the ATP content in these cells. Additionally, the viable cells in the reaction suspension decreased by about 40% after incubation with 30 mM NaF for 15 min. Observing these leukocytes treated with NaF by optical microscopy, swelling of the cell and an alteration of the nuclei form occurred. On the basis of these results, we speculated that the increased THP transport in polymorphonuclear leukocytes by NaF, probably F-, might be due, at least in part, to an alteration of the morphological form.
我们先前发现，吡柔比星（THP）可通过载体介导的转运系统被大鼠多形核白细胞主动摄取。在代谢抑制剂的作用实验中，鱼藤酮、2,4-二硝基苯酚和氰化钠显著降低了THP的转运。然而，氟化钠（NaF）显著增加了摄取量，这一结果与一些报道不同。因此，我们研究了NaF对白细胞摄取THP的作用，以阐明NaF对药物转运影响的差异。30 mM NaF对细胞摄取THP的促进作用有一个最佳作用时间（15 - 20分钟），且呈浓度依赖性（5 - 30 mM）。30 mM氟化钾与NaF一样，增加了摄取量。另一方面，NaF（5 - 30 mM）剂量依赖性地降低了这些细胞中的ATP含量。此外，在30 mM NaF孵育15分钟后，反应悬液中的活细胞减少了约40%。通过光学显微镜观察这些用NaF处理的白细胞，发现细胞肿胀且细胞核形态发生改变。基于这些结果，我们推测NaF（可能是F-）使多形核白细胞中THP转运增加，至少部分原因可能是形态学形式的改变。
