Regulation of the multidrug resistance genes by stress signals

J Pharm Pharm Sci. May-Aug 2000;3(2):268-80.

Abstract

Transporters in the body play a large role in the distribution and elimination of many clinically important therapeutic substances. Of these, perhaps the one that has been best studied is P-Glycoprotein (PGP), a 170 kDa membrane-bound protein which has been implicated as a primary cause of multidrug-resistance in tumors. An understanding of the physiological regulation of these transporters is key to designing strategies for the improvement of therapeutic efficacy of drugs which are their substrates. To that end, we examine herein the current state of understanding of the molecular regulation of PGP by a variety of endogenous and environmental stimuli which evoke stress responses including cytotoxic agents, heat shock, irradiation, genotoxic stress, inflammation, inflammatory mediators, cytokines and growth factors.

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 Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism
  • Animals
  • Cytokines / metabolism
  • DNA Damage
  • Drug Resistance, Multiple*
  • Gene Expression Regulation*
  • Growth Substances / metabolism
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism
  • Humans
  • Inflammation Mediators / metabolism
  • Multidrug Resistance-Associated Proteins
  • Radiation, Ionizing
  • Signal Transduction*

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP-Binding Cassette Transporters
  • Cytokines
  • Growth Substances
  • Heat-Shock Proteins
  • Inflammation Mediators
  • Multidrug Resistance-Associated Proteins