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首页> 外文期刊>Journal of Cellular Physiology >Effects of hypotonic and hypoionic media on drug pumping by P-glycoprotein expressed in epithelial and nonepithelial cell lines.
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Effects of hypotonic and hypoionic media on drug pumping by P-glycoprotein expressed in epithelial and nonepithelial cell lines.

机译:低渗和hypoionic媒体对药物的影响泵由22上皮中表达和nonepithelial细胞系。

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The effects of anisotonic and anisoionic media on the drug-pumping function of P-glycoprotein (Pgp) were studied in epithelial and nonepithelial cells. We used HT-29 colon cells (HT-29/Pgp-) induced to express Pgp and MDR phenotype (HT-29/Pgp+) and NIH3T3 (3T3/Pgp-) cells which were stably transfected with human MDR1 DNA (3T3/Pgp+). Intracellular concentrations of rhodamine 123 (R-123) preloaded into cells were monitored as a function of time by fluorescence imaging microscopy, while cells were superfused with media of different tonicity and/or ionic strength. Efflux was analyzed by a single exponential decay function. In all media tested efflux was considerably higher in Pgp+ than Pgp- cells. In both HT-29 and 3T3 cells loaded with dye in isotonic conditions, dye efflux was not significantly different whether it was measured in isoionic-isotonic (130 mM NaCl, 300 mOsm), hypoionic-isotonic (87 mM NaCl), or hypoionic-hypotonic (200, 150, or 100 mOsm) media throughout the entire experiment or whether themedia were changed during the experiment. Similar results were obtained when cells were preincubated and preloaded with dye under hypotonic conditions. Under extreme hypotonic and hypoionic challenge (changing from 130 mM NaCl-300 mOsm to 43 mM NaCl-100 mOsm medium), 3T3 cells, but not HT-29 cells, underwent marked shape and size changes which reduced R-123 cell-associated fluorescence. The changes were most conspicuous in Pgp+ cells, possibly reflecting a Pgp effect on the osmotic or osmoregulatory properties of the cells. However, drug-pumping activity remained essentially unimpaired even under the most extreme hypotonic/hypoionic conditions.
机译:anisotonic和anisoionic媒体的影响22的drug-pumping功能(Pgp)研究了在上皮和nonepithelial细胞。诱导表达Pgp和MDR表型稳定转染DNA与人类凋亡(3 t3 / Pgp +)。罗丹明123 (r - 123)加载到细胞荧光监控作为时间的函数成像显微镜,而细胞被过冷与媒体不同的强壮和/或离子的力量。指数衰减函数。射流在Pgp +比Pgp -相当高细胞。染料在等渗条件下,染料流出不是是否测量了明显不同在isoionic-isotonic(130毫米氯化钠300 mOsm),hypoionic-isotonic氯化钠(87毫米),或hypoionic-hypotonic(200、150、或100 mOsm)媒体还是在整个实验媒体在实验中改变。当细胞中得到了相似的结果preincubated预加载和染料低渗的条件。hypoionic挑战(从130毫米氯化钠- 300 mOsm 43毫米氯化钠- 100 mOsm介质),3 t3细胞,但不是HT-29细胞,进行了标记形状和大小的变化,减少了r - 123细胞相关荧光。最明显的在Pgp +细胞,可能反映了Pgp对渗透性的影响细胞的渗透调节的特性。drug-pumping活动依然在本质上是没有即使在最极端低渗的/ hypoionic条件。

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