The Physiological Function of Drug-Transporting P-glycoproteins

Semin Cancer Biol. 1997 Jun;8(3):161-70. doi: 10.1006/scbi.1997.0068.

Abstract

The mammalian drug-transporting or mdr1-type P-glycoproteins can extrude a range of structurally diverse, toxic xenobiotic compounds from cells. Our analysis of knockout mice lacking one or both of the mdr1-type P-glycoproteins indicates that a major function of these proteins is the protection of organisms against many of the toxic xenobiotics to which they can potentially be exposed in nature. P-glycoprotein confers protection by limiting the uptake of compounds from the gastrointestinal tract, and by stimulating excretion of compounds in the liver, kidney, and intestine. Moreover, P-glycoprotein in the blood-brain barrier and other blood-tissue barriers protects sensitive organs from exposure to toxic compounds that may have entered the bloodstream. Although we cannot exclude additional physiological functions for mdr1-type P-glycoproteins, these are not vital, since the mdr1-deficient mice are viable and fertile, and do not display obvious phenotypic abnormalities other than hypersensitivity to drugs.

Publication types

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

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / physiology*
  • Animals
  • Biological Transport, Active / physiology
  • Blood-Brain Barrier
  • Drug Resistance, Multiple
  • Humans
  • Mice
  • Pharmacokinetics

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1