Abstract
Probenecid is used as a uricosuric agent in the treatment of chronic gout and as an adjunct to enhance antibiotic levels in the blood. For research purposes, it is used as a prototypic inhibitor of organic anion transporters and MRPs, including MPR2. The purpose of this research is to study the interaction of probenecid with two other important transporters of the ATP-binding cassette family, Breast Cancer Resistance Protein (BCRP) and P-glycoprotein. These drug efflux transporters are present in the intestine, liver and other organs, and they affect the bioavailability of many compounds. Using the polarized canine kidney cell line MDCK-II and its human MDR1-, BCRP- and murine Bcrp1-transduced subclones, we found that probenecid is transported by mouse Bcrp1 and human BCRP, but not by P-glycoprotein. In addition, flow cytometry experiments showed that probenecid did not affect the accumulation of mitoxantrone in Bcrp1- and BCRPtransduced cells, indicating that this compound was not an effective BCRP/Bcrp1 inhibitor at the concentrations used. We conclude that probenecid is a good substrate of BCRP/Bcrp1, suggesting potential interaction with BCRP/Bcrp1 inhibitors.
Keywords: Probenecid, Breast Cancer Resistance Protein, P-glycoprotein, transport, inhibition
Letters in Drug Design & Discovery
Title: Interaction of Probenecid with the Breast Cancer Resistance Protein Transporter (BCRP/ABCG2)
Volume: 3 Issue: 4
Author(s): G. Merino, R. Real, A. J. Molina, M. M. Pulido, J. G. Prieto and A. I. Alvarez
Affiliation:
Keywords: Probenecid, Breast Cancer Resistance Protein, P-glycoprotein, transport, inhibition
Abstract: Probenecid is used as a uricosuric agent in the treatment of chronic gout and as an adjunct to enhance antibiotic levels in the blood. For research purposes, it is used as a prototypic inhibitor of organic anion transporters and MRPs, including MPR2. The purpose of this research is to study the interaction of probenecid with two other important transporters of the ATP-binding cassette family, Breast Cancer Resistance Protein (BCRP) and P-glycoprotein. These drug efflux transporters are present in the intestine, liver and other organs, and they affect the bioavailability of many compounds. Using the polarized canine kidney cell line MDCK-II and its human MDR1-, BCRP- and murine Bcrp1-transduced subclones, we found that probenecid is transported by mouse Bcrp1 and human BCRP, but not by P-glycoprotein. In addition, flow cytometry experiments showed that probenecid did not affect the accumulation of mitoxantrone in Bcrp1- and BCRPtransduced cells, indicating that this compound was not an effective BCRP/Bcrp1 inhibitor at the concentrations used. We conclude that probenecid is a good substrate of BCRP/Bcrp1, suggesting potential interaction with BCRP/Bcrp1 inhibitors.
Export Options
About this article
Cite this article as:
Merino G., Real R., Molina J. A., Pulido M. M., Prieto G. J. and Alvarez I. A., Interaction of Probenecid with the Breast Cancer Resistance Protein Transporter (BCRP/ABCG2), Letters in Drug Design & Discovery 2006; 3 (4) . https://dx.doi.org/10.2174/157018006776743170
DOI https://dx.doi.org/10.2174/157018006776743170 |
Print ISSN 1570-1808 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-628X |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Synthesis of Aryl-Substituted Naphthalenoids as Potent Topoisomerase Inhibitors
Medicinal Chemistry Silencing the Transcription Factor FOSL1 in Hyperproliferative HaCaT Cells Makes Them Susceptible to IFN-γ
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Curcumin: A Promising Agent Targeting Cancer Stem Cells
Anti-Cancer Agents in Medicinal Chemistry Colon Targeted Rifaximin Nanosuspension for the Treatment of Inflammatory Bowel Disease (IBD)
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Restoration of Antitumor Immunity Through Selective Inhibition of Myeloid Derived Suppressor Cells by Anticancer Therapies
Current Molecular Medicine Application of Nanocellulose Derivatives as Drug Carriers; A Novel Approach in Drug Delivery
Anti-Cancer Agents in Medicinal Chemistry Functionalized Magnetic Nanostructures for Anticancer Therapy
Current Drug Targets Suberosin Attenuates the Proliferation of MCF-7 Breast Cancer Cells in Combination with Radiotherapy or Hyperthermia
Current Drug Research Reviews Optimizing Antitumor Efficacy and Adverse Effects of Pegylated Liposomal Doxorubicin by Scheduled Plasmapheresis: Impact of Timing and Dosing
Current Drug Delivery From Test Tube to Clinical Trial; Promising Herbs with NF-κB and COX- 2 Activity
Current Immunology Reviews (Discontinued) Modulation of ABC Transporters by Nuclear Receptors: Physiological, Pathological and Pharmacological Aspects
Current Medicinal Chemistry Adult Retinal Ganglion Cell Axon Regeneration and Re-innervation
Current Tissue Engineering (Discontinued) Electrochemical Evaluation of the Total Antioxidant Capacity of Yam Food Samples on a Polyglycine-Glassy Carbon Modified Electrode
Current Analytical Chemistry Signaling Pathways that Regulate Basal ABC Transporter Activity at the Blood- Brain Barrier
Current Pharmaceutical Design Hereditary Breast Cancer in Sub-Saharan Africa
Current Women`s Health Reviews The Role of Metabolizing Enzymes and Transporters in Antiretroviral Therapy
Current Topics in Medicinal Chemistry Peptides for Diagnosis and Treatment of Colorectal Cancer
Current Medicinal Chemistry The Pathway Less Traveled: Moving from Candidate Genes to Candidate Pathways in the Analysis of Genome-Wide Data from Large Scale Pharmacogenetic Association Studies
Current Pharmacogenomics and Personalized Medicine TRAIL: A Sword for Killing Tumors
Current Medicinal Chemistry Current Biological Therapies for Inflammatory Bowel Disease
Current Pharmaceutical Design