TY - JOUR
T1 - Differential transport properties of two mdr gene products are distinguished by progesterone
AU - Yang, Chia Ping Huang
AU - Cohen, Dalia
AU - Greenberger, Lee M.
AU - Hsu, Stephen I.H.
AU - Horwitz, Susan Band
PY - 1990/6/25
Y1 - 1990/6/25
N2 - P-glycoprotein is an integral membrane protein that is overproduced in multidrug-resistant cells. It is likely to function as an energy-dependent drug efflux pump to maintain intracellular drug concentrations below cytotoxic levels. Individually isolated multidrug-resistant murine cell lines, J7.V1-1 and J7.V3-1, over-produce P-glycoproteins encoded by the mdr1b and mdr1a genes, respectively. The transport properties of these cell lines and the drug binding characteristics of their P-glycoproteins have been compared. It is concluded that 1) the mdr1a gene product is a more efficient efflux pump than the mdr1b gene product, and 2) whereas a single class of vinblastine binding sites is present in J7.V1-1 membrane vesicles, there appears to be two classes of such sites in J7.V3-1 membrane vesicles. The effects of verapamil and progesterone, two compounds that are known to interact with P-glycoprotein, have been analyzed in the two cell lines. Progesterone inhibited drug binding and efflux and increased drug sensitivity to vinblastine with more potency in J7.V1-1 cells than in J7.V3-1 cells. It is concluded that progesterone, but not verapamil, can be used to differentiate the two mdr gene products in the mouse.
AB - P-glycoprotein is an integral membrane protein that is overproduced in multidrug-resistant cells. It is likely to function as an energy-dependent drug efflux pump to maintain intracellular drug concentrations below cytotoxic levels. Individually isolated multidrug-resistant murine cell lines, J7.V1-1 and J7.V3-1, over-produce P-glycoproteins encoded by the mdr1b and mdr1a genes, respectively. The transport properties of these cell lines and the drug binding characteristics of their P-glycoproteins have been compared. It is concluded that 1) the mdr1a gene product is a more efficient efflux pump than the mdr1b gene product, and 2) whereas a single class of vinblastine binding sites is present in J7.V1-1 membrane vesicles, there appears to be two classes of such sites in J7.V3-1 membrane vesicles. The effects of verapamil and progesterone, two compounds that are known to interact with P-glycoprotein, have been analyzed in the two cell lines. Progesterone inhibited drug binding and efflux and increased drug sensitivity to vinblastine with more potency in J7.V1-1 cells than in J7.V3-1 cells. It is concluded that progesterone, but not verapamil, can be used to differentiate the two mdr gene products in the mouse.
UR - http://www.scopus.com/inward/record.url?scp=0025316847&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0025316847&partnerID=8YFLogxK
M3 - Article
C2 - 1972378
AN - SCOPUS:0025316847
SN - 0021-9258
VL - 265
SP - 10282
EP - 10288
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 18
ER -