Jason R. Richardson and Lauren M. Aleksunes contributed equally as corresponding authors.
Inhibition of Human MDR1 and BCRP Transporter ATPase Activity by Organochlorine and Pyrethroid Insecticides
Article first published online: 20 NOV 2012
© 2012 Wiley Periodicals, Inc.
Journal of Biochemical and Molecular Toxicology
Special Issue: Special Issue 2: National Institute of Environmental Health Sciences Outstanding New Environmental Scientist Program
Volume 27, Issue 2, pages 157–164, February 2013
How to Cite
Bircsak, K. M., Richardson, J. R. and Aleksunes, L. M. (2013), Inhibition of Human MDR1 and BCRP Transporter ATPase Activity by Organochlorine and Pyrethroid Insecticides. J. Biochem. Mol. Toxicol., 27: 157–164. doi: 10.1002/jbt.21458
Contract Grant Sponsor: National Institutes of Health Institute of Diabetes and Digestive and Kidney Diseases.Contract Grant number: DK0807741.Contract Grant Sponsor: National Institutes of Health Environmental Health Sciences.Contract Grant numbers: ES020522, ES015991, ES007148.Contract Grant Sponsor: NIEHS Center for Environmental Exposures and Disease.Contract Grant number: P30ES005022.
- Issue published online: 18 FEB 2013
- Article first published online: 20 NOV 2012
- Manuscript Accepted: 13 OCT 2012
- Manuscript Revised: 4 OCT 2012
- Manuscript Received: 30 JUN 2012
- National Institutes of Health Institute of Diabetes and Digestive and Kidney Diseases. Grant Number: DK0807741
- National Institutes of Health Environmental Health Sciences. Grant Numbers: ES020522, ES015991, ES007148
- NIEHS Center for Environmental Exposures and Disease. Grant Number: P30ES005022
Despite the growing evidence suggesting that pesticides contribute to chronic diseases, there is a limited understanding of how these chemicals are removed from cells and whether pesticides can alter the disposition of drugs. The present study examined the effects of two classes of insecticides (organochlorine and pyrethroid) on the ATPase activity of the human multidrug resistance protein 1 (MDR1) and breast cancer resistance protein (BCRP) efflux transporters. Using plasma membranes from cells overexpressing MDR1 and BCRP, it was demonstrated that the organochlorine pesticide dichlorodiphenyltrichloroethane (DDT) (o,p'-DDT and p,p'-DDT isomers) as well as its metabolite (p,p'-dichlorodiphenyldichloroethane), inhibit both MDR1 and BCRP ATPase activity. In addition, p,p'-dichlorodiphenyldichloroethylene, and two pyrethroid pesticides inhibited BCRP ATPase activity between 4 and 7 μM. Additional research is necessary to further characterize the functional inhibition of MDR1 and BCRP activity and determine whether pesticides alter the transporter-mediated disposition of other chemicals. © 2012 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:157-164, 2013; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.21458