HIV-1 protease inhibitors are substrates for the MDR1 multidrug transporter

Biochemistry
C G LeeS Dey

Abstract

The FDA approved HIV-1 protease inhibitors, ritonavir, saquinavir, and indinavir, are very effective in inhibiting HIV-1 replication, but their long-term efficacy is unknown. Since in vivo efficacy depends on access of these drugs to intracellular sites where HIV-1 replicates, we determined whether these protease inhibitors are recognized by the MDR1 multidrug transporter (P-glycoprotein, or P-gp), thereby reducing their intracellular accumulation. In vitro studies in isolated membrane preparations from insect cells infected with MDR1-expressing recombinant baculovirus showed that these inhibitors significantly stimulated P-gp-specific ATPase activity and that this stimulation was inhibited by SDZ PSC 833, a potent inhibitor of P-gp. Furthermore, photoaffinity labeling of P-gp with the substrate analogue [125I]iodoarylazidoprazosin (IAAP) was inhibited by all three inhibitors. Cell-based approaches to evaluate the ability of these protease inhibitors to compete for transport of known P-gp substrates showed that all three HIV-1 protease inhibitors were capable of inhibiting the transport of some of the known P-gp substrates but their effects were generally weaker than other documented P-gp modulators such as verapamil or cyclosp...Continue Reading

References

Sep 1, 1990·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·C Cordon-CardoM R Melamed
Jul 1, 1991·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·J E Merrill, I S Chen
Jan 1, 1990·Annual Review of Immunology·M S MeltzerH E Gendelman
Oct 9, 1995·International Journal of Cancer. Journal International Du Cancer·A D Didier, F Loor
Jan 1, 1993·Annual Review of Biochemistry·M M Gottesman, I Pastan
Jan 1, 1995·Annual Review of Genetics·M M GottesmanI Pastan

❮ Previous
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Citations

Feb 4, 2006·The Journal of Membrane Biology·T W Loo, D M Clarke
Sep 2, 2005·Cancer Chemotherapy and Pharmacology·Christian ZimmermannJuergen Drewe
May 13, 2006·Journal of Bioenergetics and Biomembranes·Tip W LooDavid M Clarke
Dec 6, 2011·Archives of Pharmacal Research·Hee-Doo Yoo, Yong-Bok Lee
Dec 6, 2011·Archives of Pharmacal Research·Hyo-Kyung Han
Mar 23, 2004·Biochemical and Biophysical Research Communications·Joachim TroostJohanna Weiss
May 11, 2013·European Journal of Pharmacology·Rajni A JibodhJan H M Schellens
Oct 8, 2013·Journal of Molecular Graphics & Modelling·Gabriel E JaraAdriana B Pierini
Jan 5, 2002·Leukemia Research·Anil TulpuleAlexandra M Levine
Oct 31, 2002·Advanced Drug Delivery Reviews·Martin F Fromm
Jun 6, 2000·Advanced Drug Delivery Reviews·X Li, W K Chan
Jun 6, 2000·Advanced Drug Delivery Reviews·G C Williams, P J Sinko
Mar 17, 2000·Journal of Pharmaceutical and Biomedical Analysis·M R FizzanoM Cianfriglia
Nov 25, 2000·International Journal of Antimicrobial Agents·O TurrizianiF Dianzani
Aug 7, 2003·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Manthena V S VarmaRamesh Panchagnula
Jun 28, 2003·Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology·John G Gerber, Edward P Acosta
Jul 10, 2003·Lancet Neurology·Eain M Cornford, Marcia E Cornford
Aug 27, 2011·Journal of the American Chemical Society·Hilda A NamanjaJean Chmielewski
Mar 7, 2006·Nature Reviews. Drug Discovery·Gergely SzakácsMichael M Gottesman
Dec 16, 2005·Cell Research·J Roberto TrujilloRobert C Gallo
Mar 27, 2002·The Pharmacogenomics Journal·U Brinkmann, M Eichelbaum
Mar 23, 2002·The Pharmacogenomics Journal·M Pirmohamed, D J Back
Feb 19, 2002·British Journal of Clinical Pharmacology·Martina HennessyJ Feely
Apr 25, 2001·British Journal of Clinical Pharmacology·D J BackC Merry
Dec 12, 2001·HIV Medicine·S Taylor, A Pereira
Mar 29, 2001·The New England Journal of Medicine·S C Piscitelli, K D Gallicano
Mar 14, 2002·Proceedings of the National Academy of Sciences of the United States of America·Tip W Loo, David M Clarke
May 16, 2002·Proceedings of the National Academy of Sciences of the United States of America·Antonio ValentinGeorge N Pavlakis
Jun 22, 2000·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·J G Gerber
Jun 19, 2004·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Erin QuirkWilliam Powderly
Jan 12, 2010·AIDS Research and Human Retroviruses·Antonio ValentinGeorge N Pavlakis
Sep 8, 2010·The Journal of Antimicrobial Chemotherapy·Sonja Katharina KönigJohanna Weiss

❮ Previous
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