pH regulation in sensitive and multidrug resistant Ehrlich ascites tumor cells

被引:20
作者
Litman, T
Pedersen, SF
Kramhoft, B
Skovsgaard, T
Hoffmann, EK
机构
[1] August Krogh Inst, Dept Biochem, DK-2100 Copenhagen, Denmark
[2] Panum Inst, Dept Med Physiol, Copenhagen, Denmark
[3] Univ Copenhagen, Herlev Hosp, Dept Oncol, Copenhagen, Denmark
[4] Carlsberg Lab, Dept Chem, DK-2500 Copenhagen, Denmark
关键词
multidrug resistance; P-glycoprotein; intracellular pH; acidification; glucose; Na(+)/H(+) exchanger; H(+) efflux;
D O I
10.1159/000016277
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Maintenance and regulation of intracellular pH (pH(i)) was studied in wild-type Ehrlich ascites tumor cells (EHR2) and five progressively daunorubicin-resistant, P-glycoprotein (P-gp)-expressing strains, the maximally resistant of which is EHR2/1.3. Steady-state pH(i) was similar in cells expressing different amounts of P-gp, in the absence and presence of glucose. In EHR2/1.3, glucose-induced acidification was reduced, and proton efflux was increased, compared to the wild-type EHR2, differences which were not caused by increased activity of a Na(+)/H(+) exchanger in the resistant cells. Comparing all six cell lines, no evidence was found for a correlation between the amount of P-gp in the membrane and pH(i) regulation, which was also unaffected by P-gp modulators. However, a correlation was seen between relative resistance/daunorubicin accumulation and acid extrusion rate, which is likely to be due to aspects of development of drug resistance other than P-gp.
引用
收藏
页码:138 / 150
页数:13
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