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首页> 外文期刊>Journal of Cellular Physiology >Lysosomotropic agents increase vinblastine efflux from mouse MDR proximal kidney cells exhibiting vectorial drug transport.
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Lysosomotropic agents increase vinblastine efflux from mouse MDR proximal kidney cells exhibiting vectorial drug transport.

机译：Lysosomotropic代理商提高长春花碱流出从鼠标MDR近端肾细胞表现出矢量毒品运输。

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Vinblastine (VBL) transport and efflux were studied in mouse proximal tubule PKSV-PR cells and in their multidrug-resistant derivatives PKSV-PRcol50 cells. The PKSV-PRcol50 cells produced more mdr1b transcripts and had higher resistance to various drugs. PKSV-PRcol50 cells had a predominantly basal-to-apical flux of [3H]VBL, 2.7 times larger than that in PKSV-PR cells. This flux was partially inhibited by verapamil (VRP) (10 microM) and cyclosporin A (CsA) (200 nM). [3H]VBL efflux was also greater in PKSV-PRcol50 than in PKSV-PR cells. Treatment with NH4Cl (30 mM), a lysosomotropic weak base, and concanamycin A (CCM A) (20 nM), an inhibitor of the vacuolar H+/ATPase, further increased [3H]VBL efflux from PKSV-PRcol50 cells. The cytoplasmic pH (pHcyt) of these drug-resistant cells transiently increased in the presence of NH4Cl deltapHcyt: +0.4). CCM A caused a moderate, delayed increase in pHcyt (deltapHcyt: +0.1) and made the acidic intralysosomal compartment more alkaline (deltapHlys: +1.3). VRP and CsA prevented the NH4Cl- and CCM A-induced [3H]VBL efflux from PKSV-PRcol50 cells. However, VRP (10 microM) did not significantly affect pHcyt of PKSV-PRcol50 cells, the NH4Cl-and CCM A-induced pHcyt responses, and the effect of CCMA on pHlys. Thus, lysosomotropic agents may affect the kinetics of [3H]VBL efflux. Our results also suggest that the inhibitory action of VRP on VBL efflux was not directly mediated by a pH-dependent process in these drug-resistant renal proximal tubule cells.
机译：长春花碱(轮式侦察车的)运输和流出研究老鼠近端小管PKSV-PR细胞和耐多药衍生品产生更多mdr1b成绩单和更高抵抗各种药物。有一个主要basal-to-apical通量的[3 h]轮式侦察车,2.7倍PKSV-PR细胞。维拉帕米(VRP) (10 microM)和环孢菌素A(CsA)(200海里)。在PKSV-PRcol50 PKSV-PR细胞。与NH4Cl(30毫米),lysosomotropic弱碱,和concanamycin (CCM) (20 nM)抑制剂空泡的H + / atp酶,进一步增加从PKSV-PRcol50细胞[3 h]轮式侦察车的流出。这些耐药的细胞质pH值(pHcyt)细胞是暂时性的增加NH4Cl deltapHcyt: + 0.4)。延迟增加pHcyt (deltapHcyt: + 0.1)使酸性intralysosomal隔间防止NH4Cl - CCM A-induced [3 h]轮式侦察车从PKSV-PRcol50流出细胞。的pHcyt microM)没有显著影响NH4Cl-and CCM A-induced PKSV-PRcol50细胞pHcyt回应,pHlys CCMA的效果。因此,lysosomotropic代理可能影响动力学[3 h]轮式侦察车的流出。建议在轮式侦察车的VRP的抑制作用流出并不是直接由在这些耐药pH-dependent过程肾近端小管细胞。

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