Journal ArticleDOI
Multidrug resistance protein 4 (MRP4/ABCC4): a versatile efflux transporter for drugs and signalling molecules
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TLDR
The unique structure, regulation and dual localisation of MRP4 in polarised cells could be connected with a key function in cellular protection and extracellular signalling pathways.About:
This article is published in Trends in Pharmacological Sciences.The article was published on 2008-04-01. It has received 378 citations till now. The article focuses on the topics: Multidrug Resistance-Associated Proteins & Multidrug resistance-associated protein 2.read more
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OtherDOI
Bile formation and secretion.
TL;DR: Canalicular bile secretion is determined by both bile salt-dependent and independent transport systems which are localized at the apical membrane of the hepatocyte and largely consist of a series of adenosine triphosphate-binding cassette transport proteins that function as export pumps for bile salts and other organic solutes.
Journal ArticleDOI
Foxa1 and Foxa2 Are Essential for Sexual Dimorphism in Liver Cancer
TL;DR: It is discovered that sexually dimorphic HCC is completely reversed in Foxa1- and Foxa2-deficient mice after diethylnitrosamine-induced hepatocarcinogenesis, and single nucleotide polymorphisms at FOXA2 binding sites reduce binding of both FOXa2 and ERα to their targets in human liver and correlate with HCC development in women.
Journal ArticleDOI
Emerging transporters of clinical importance: an update from the International Transporter Consortium.
Kathleen M. Hillgren,Dietrich Keppler,Arik A. Zur,Kathleen M. Giacomini,Bruno Stieger,C E Cass,Lei Zhang +6 more
TL;DR: Additional transporters of emerging importance in pharmacokinetics, interference of drugs with transport of endogenous compounds, and drug–drug interactions (DDIs) in humans are identified.
Journal ArticleDOI
Drug Transporters in Drug Efficacy and Toxicity
TL;DR: Transporters of the solute carrier and ATP-binding cassette superfamilies are reviewed to outline how understanding the expression, function, and genetic variation in such drug transporters will result in better strategies for optimal drug design and tissue targeting as well as reduce the risk for drug-drug interactions and adverse drug responses.
Book ChapterDOI
Multidrug resistance proteins (MRPs, ABCCs): importance for pathophysiology and drug therapy.
TL;DR: The role of MRP subfamily members in pathophysiology may be illustrated by the MRP-mediated release of proinflammatory and immunomodulatory mediators such as leukotrienes and prostanoids.
References
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Journal ArticleDOI
Structure of a bacterial multidrug ABC transporter
TL;DR: The observed, outward-facing conformation reflects the ATP-bound state, with the two nucleotide-binding domains in close contact and the two transmembrane domains forming a central cavity—presumably the drug translocation pathway—that is shielded from the inner leaflet of the lipid bilayer and from the cytoplasm, but exposed to the outer leaflet and the extracellular space.
Journal ArticleDOI
Transmembrane transport of endo- and xenobiotics by mammalian ATP-binding cassette multidrug resistance proteins
TL;DR: What is known of the structure of the MRPs and the mechanisms by which they recognize and transport their diverse substrates are described and evidence that they may be involved in the clinical drug resistance of various forms of cancer is summarized.
Journal ArticleDOI
MRP4: A previously unidentified factor in resistance to nucleoside-based antiviral drugs.
John D. Schuetz,Michele Connelly,Daxi Sun,Sheela G. Paibir,Patricia M. Flynn,R V Srinivas,Alok Kumar,Arnold Fridland +7 more
TL;DR: In the study of alternative or additional mechanisms of resistance operating during antiviral therapy, overexpression and amplification of the MRP4 gene correlated with ATP-dependent efflux of PMEA and azidothymidine monophosphate from cells and, thus, with resistance to these drugs.
Journal ArticleDOI
The MRP4/ABCC4 Gene Encodes a Novel Apical Organic Anion Transporter in Human Kidney Proximal Tubules: Putative Efflux Pump for Urinary cAMP and cGMP
Rémon A. M. H. Van Aubel,Pascal H. E. Smeets,Janny G. P. Peters,René J. M. Bindels,Frans G. M. Russel +4 more
TL;DR: MRP4 is a novel apical organic anion transporter and the putative efflux pump for cAMP and cGMP in human kidney proximal tubules and in kidneys of rats deficient in the apical anionic conjugate efflux Pump Mrp2, Mrp4 expression is maintained at the same level.
Journal ArticleDOI
The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs.
Glen Reid,Pieter Roeland Wielinga,Noam Zelcer,Ingrid van der Heijden,Annemieke Kuil,Marcel de Haas,Jan Wijnholds,Piet Borst +7 more
TL;DR: Investigation of the interaction between prostaglandins and members of the ATP-binding cassette (ABC) transporter ABCC [multidrug resistance protein (MRP)] family of membrane export pumps suggests that MRP4 can release prostaglandsins from cells, and that some nonsteroidal antiinflammatory drugs might also act by inhibiting this release.