Differential transport properties of two mdr gene products are distinguished by progesterone

Chia-Ping H. Yang, Dalia Cohen, Lee M. Greenberger, Stephen I H Hsu, Susan Band Horwitz

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)10282-10288
Number of pages7
JournalJournal of Biological Chemistry
Volume265
Issue number18
StatePublished - Jun 25 1990

Fingerprint

Transport properties
Progesterone
Genes
P-Glycoproteins
Pharmaceutical Preparations
Vinblastine
Cells
P-Glycoprotein
Verapamil
Cell Line
Pumps
Membranes
Membrane Proteins
Binding Sites

ASJC Scopus subject areas

  • Biochemistry

Cite this

Differential transport properties of two mdr gene products are distinguished by progesterone. / Yang, Chia-Ping H.; Cohen, Dalia; Greenberger, Lee M.; Hsu, Stephen I H; Band Horwitz, Susan.

In: Journal of Biological Chemistry, Vol. 265, No. 18, 25.06.1990, p. 10282-10288.

Research output: Contribution to journalArticle

Yang, Chia-Ping H. ; Cohen, Dalia ; Greenberger, Lee M. ; Hsu, Stephen I H ; Band Horwitz, Susan. / Differential transport properties of two mdr gene products are distinguished by progesterone. In: Journal of Biological Chemistry. 1990 ; Vol. 265, No. 18. pp. 10282-10288.
@article{1745501d74dd4ac0af347b34de5fef3f,
title = "Differential transport properties of two mdr gene products are distinguished by progesterone",
abstract = "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.",
author = "Yang, {Chia-Ping H.} and Dalia Cohen and Greenberger, {Lee M.} and Hsu, {Stephen I H} and {Band Horwitz}, Susan",
year = "1990",
month = "6",
day = "25",
language = "English (US)",
volume = "265",
pages = "10282--10288",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "18",

}

TY - JOUR

T1 - Differential transport properties of two mdr gene products are distinguished by progesterone

AU - Yang, Chia-Ping H.

AU - Cohen, Dalia

AU - Greenberger, Lee M.

AU - Hsu, Stephen I H

AU - Band Horwitz, Susan

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

VL - 265

SP - 10282

EP - 10288

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 18

ER -