The multidrug resistance (mdr1) gene product functions as an ATP channel

Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):312-6. doi: 10.1073/pnas.90.1.312.

Abstract

The multidrug resistance (mdr1) gene product, P-glycoprotein, is responsible for the ATP-dependent extrusion of a variety of compounds, including chemotherapeutic drugs, from cells. The data presented here show that cells with increased levels of the P-glycoprotein release ATP to the medium in proportion to the concentration of the protein in their plasma membrane. Furthermore, measurements of whole-cell and single-channel currents with patch-clamp electrodes indicate that the P-glycoprotein serves as an ATP-conducting channel in the plasma membrane. These findings suggest an unusual role for the P-glycoprotein.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Adenosine Triphosphate / metabolism*
  • Amino Acid Sequence
  • Animals
  • Antibodies
  • CHO Cells
  • Cell Membrane / physiology
  • Cricetinae
  • Drug Resistance / genetics*
  • Humans
  • Ion Channels / physiology*
  • Lung Neoplasms
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology*
  • Mice
  • Molecular Sequence Data
  • Peptides / immunology
  • Recombinant Fusion Proteins / metabolism
  • Transfection
  • Tumor Cells, Cultured

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antibodies
  • Ion Channels
  • Membrane Glycoproteins
  • Peptides
  • Recombinant Fusion Proteins
  • Adenosine Triphosphate