ArticleInvestigative ophthalmology & visual science2013
MRP4-mediated regulation of intracellular cAMP and cGMP levels in trabecular meshwork cells and homeostasis of intraocular pressure.
Article in Investigative ophthalmology & visual science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Influence of PTGS1, PTGFR, and MRP4 genetic variants on intraocular pressure response to latanoprost in Chinese primary open-angle glaucoma patients.European journal of clinical pharmacology · 2015Trial
- Identification and Validation of Key Biomarkers in the Proximal Aqueous Humor Outflow Pathway.Current issues in molecular biology · 2025Article
- Candidate SNP Markers Significantly Altering the Affinity of the TATA-Binding Protein for the Promoters of Human Genes Associated with Primary Open-Angle Glaucoma.International journal of molecular sciences · 2024Article
- Clinical pharmacology and pharmacogenetics of prostaglandin analogues in glaucoma.Frontiers in pharmacology · 2022Review
- Cyclic Nucleotide (cNMP) Analogues: Past, Present and Future.International journal of molecular sciences · 2021Review
- Xeno- and Feeder-Free Differentiation of Human iPSCs to Trabecular Meshwork-Like Cells by Recombinant Cytokines.Translational vision science & technology · 2021Article
- Review
- Cyclic AMP efflux through MRP4 regulates actin dynamics signalling pathway and sperm motility in bovines.Scientific reports · 2020Article
- Pressure-induced expression changes in segmental flow regions of the human trabecular meshwork.Experimental eye research · 2017Review
- Effects of Hydrogen Sulfide-Releasing Compounds on Aqueous Humor Outflow Facility in Porcine Ocular Anterior Segments, Ex Vivo.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2017Article
- The Soluble Guanylate Cyclase Stimulator IWP-953 Increases Conventional Outflow Facility in Mouse Eyes.Investigative ophthalmology & visual science · 2016Article
- Extracellular matrix in the trabecular meshwork: intraocular pressure regulation and dysregulation in glaucoma.Experimental eye research · 2015Review
- Blockade of Multidrug Resistance-Associated Proteins Aggravates Acute Pancreatitis and Blunts Atrial Natriuretic Factor's Beneficial Effect in Rats: Role of MRP4 (ABCC4).Molecular medicine (Cambridge, Mass.) · 2015Article
- ABCB1 transporter and Toll-like receptor 4 in trabecular meshwork cells.Molecular vision · 2015Article
- ABCC4 is required for cell proliferation and tumorigenesis in non-small cell lung cancer.OncoTargets and therapy · 2014Article
- Antioxidant delivery pathways in the anterior eye.BioMed research international · 2013Review
- Control of outflow resistance by soluble adenylyl cyclase.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and TherapeuticsReview
- Intraocular pressure homeostasis: maintaining balance in a high-pressure environment.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and TherapeuticsReview
- The Role of Nitric Oxide in the Intraocular Pressure Lowering Efficacy of Latanoprostene Bunod: Review of Nonclinical Studies.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and TherapeuticsReview
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
purposeMultidrug, resistance-associated protein-4 (MRP4) is a membrane transporter that regulates the cellular efflux of cyclic nucleotides (cAMP and cGMP) involved in various physiologic responses. This study examined the expression and distribution of MRP4 in the trabecular meshwork (TM) cells and its role in homeostasis of IOP.
methodsExpression and distribution of MRP4 in human TM (HTM) cells and aqueous humor (AH) outflow pathway was determined by RT-PCR, immunoblotting, and immunofluorescence. Effects of inhibiting MRP4 activity and suppression of MRP4 expression on cAMP and cGMP levels, myosin light chain (MLC) phosphorylation, actin filament organization and activity of protein kinase G (PKG), protein kinase A (PKA), Rho guanosine triphosphatase (GTPase), and MLC phosphatase was monitored in HTM cells using ELISA, siRNA, biochemical, and immunofluorescence analyses. Topical application of the MRP4 inhibitor MK571 was tested to assess changes in IOP in rabbits.
resultsRT-PCR, immunoblot, and immunofluorescence analyses confirmed the expression of MRP4 in HTM cells and distribution in human AH outflow pathway. Inhibition of MRP4 in HTM cells by MK571 or probenecid resulted in cell shape changes and decreases in actin stress fibers and MLC phosphorylation. Levels of intracellular cAMP and cGMP in HTM cells were increased significantly under these conditions. MK571-induced HTM cell relaxation appeared to be mediated predominantly via activation of the cGMP-dependent PKG signaling pathway. Topical application of MK571 significantly decreased IOP in Dutch-Belted rabbits.
conclusionsThese observations reveal that cyclic nucleotide efflux controlling transporter-MRP4 plays a significant role in IOP homeostasis potentially by regulating the relaxation characteristics of AH outflow pathway cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.