ArticlePharmaceutical research2007
Multidrug resistance protein 1 (MRP1) in rabbit conjunctival epithelial cells: its effect on drug efflux and its regulation by adenoviral infection.
Article in Pharmaceutical research, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
7 citing papers in PubMed, 26 citations in OpenAlex.
- Bile Duct Ligation Impairs Function and Expression of Mrp1 at Rat Blood-Retinal Barrier via Bilirubin-Induced P38 MAPK Pathway Activations.International journal of molecular sciences · 2022Article
- Novel Eye Drop Delivery Systems: Advance on Formulation Design Strategies Targeting Anterior and Posterior Segments of the Eye.Pharmaceutics · 2022Review
- Ocular Drug Delivery Barriers-Role of Nanocarriers in the Treatment of Anterior Segment Ocular Diseases.Pharmaceutics · 2018Review
- Article
- Mechanism of RPE cell death in α-crystallin deficient mice: a novel and critical role for MRP1-mediated GSH efflux.PloS one · 2012Article
- Ocular drug delivery.The AAPS journal · 2010Review
- Recent perspectives in ocular drug delivery.Pharmaceutical research · 2009Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
purposeTo evaluate the expression, localization, function, and regulation of multidrug resistance protein (MRP1) in rabbit conjunctival epithelial cells (RCEC). MATERIALS AND
methodsMRP1 gene expression in RCEC was determined by reverse transcription-polymerase chain reaction (RT-PCR), and MRP1 protein expression and its localization were determined by Western blot analysis and immunofluorescence using an anti-MRP1 monoclonal antibody, MRPr1. The effect of MRP1 on the transport and uptake of fluorescein was evaluated in RCEC grown on Transwell filters. Moreover, the effect of adenovirus type 5 (Ad5)-infected RCEC, and cytokines (Interleukin 1 (IL-1), IL-6, and tumor necrosis factor alpha (TNFalpha)) on MRP1 expression and leukotriene C4 (LTC4) uptake were investigated.
resultsA 652 bp RT-PCR product from rabbit conjunctiva showed a 87% homology to human MRP1. Immunostaining with MRPr1 revealed a predominant basolateral localization of MRP1 in RCEC. Uptake of fluorescein, a MRP1 substrate, was increased (203-290%) in the presence of uricosuric drug probenecid at 100 microM, anti-inflammatory drug indomethacin at 10 microM and diclofenac, flurbiprofen, and ofloxacin at 1 mM, and by ATP depletion, but not influenced by the depletion of GSH, and the presence of antiviral cidofovir and anti-inflammatory drug cromolyn and prednisolone. Apical-to-basolateral facilitated transport of LTC4 was abolished in the presence of probenecid. Western blot analysis with MRPr1 revealed a distinct band at approximately 190 kDa for freshly isolated and cultured RCEC. Both Ad5 and cytokines (IL-1, IL-6, and TNF-alpha) up-regulated MRP1 expression, thereby reducing LTC4 uptake.
conclusionsMRP1 appears to be primarily localized in the basolateral membrane of RCEC and function in the efflux of certain organic anions and inflammatory factors out of cells from the basolateral membrane. The upregulation in the expression of MRP1 by Ad5-infection and cytokines suggests a role of MRP1 in the transport of inflammatory factors during ocular inflammation. Supported by NIH grants EY12578, EY10421, and EY12356.
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