pH regulation in sensitive and multidrug resistant Ehrlich ascites tumor cells.
Maintenance and regulation of intracellular pH (pHi) 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 pHi 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 pHi 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.
Litman
T
T
Department of Medical Physiology, Panum Institute, Copenhagen, Denmark.
Pedersen
S F
SF
Kramhøft
B
B
Skovsgaard
T
T
Hoffmann
E K
EK
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002021:Buffers; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005947:Glucose / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D017136:Ion Transport; D011522:Protons; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002021:Buffers; D011522:Protons; D000584:Amiloride; D005947:Glucose