ArticleAAPS pharmSci2003
Functional differences in nucleoside and nucleobase transporters expressed on the rabbit corneal epithelial cell line (SIRC) and isolated rabbit cornea.
Article in AAPS pharmSci, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 39 citations in OpenAlex.
- From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics.Materials today. Bio · 2025Review
- Human Umbilical Cord-Derived Mesenchymal Stem Cells Promote Corneal Epithelial Repair In Vitro.Cells · 2021Article
- Functional identification of SLC43A3 as an equilibrative nucleobase transporter involved in purine salvage in mammals.Scientific reports · 2015Article
- Ganciclovir ophthalmic gel 0.15% for the treatment of acute herpetic keratitis: background, effectiveness, tolerability, safety, and future applications.Therapeutics and clinical risk management · 2014Review
- Targeted lipid based drug conjugates: a novel strategy for drug delivery.International journal of pharmaceutics · 2012Article
- Prodrug strategies in ocular drug delivery.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2012Review
- Acute Herpetic Keratitis: What is the Role for Ganciclovir Ophthalmic Gel?Ophthalmology and eye diseases · 2012Article
- Small Neutral Amino Acid Ester Prodrugs of Acyclovir Targeting Amino Acid Transporters on the Cornea: Possible Antiviral Agents Against Ocular HSV-1 Infections.Ophthalmology and eye diseases · 2010Article
- Vitreal kinetics of quinidine in rabbits in the presence of topically coadministered P-glycoprotein substrates/modulators.Drug metabolism and disposition: the biological fate of chemicals · 2009Article
- Ocular pharmacokinetics of acyclovir amino acid ester prodrugs in the anterior chamber: evaluation of their utility in treating ocular HSV infections.International journal of pharmaceutics · 2008Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The purpose of this study was to investigate the expression of nucleoside/nucleobase transporters on the Statens Seruminstitut rabbit corneal (SIRC) epithelial cell line and to evaluate SIRC as an in vitro screening tool for delineating the mechanism of corneal permeation of nucleoside analogs. SIRC cells (passages 410-425) were used to study uptake of [3H]thymidine, [3H]adenine, and [3H]ganciclovir. Transport of [3H]adenine and [3H]ganciclovir was studied across isolated rabbit cornea. Uptake and transport studies were performed for 2 minutes and 120 minutes, respectively, at 34 degrees C. Thymidine uptake by SIRC displayed saturable kinetics (K(m) = 595.9 +/- 80.4 microM, and V(max) = 289.5 +/- 17.2 pmol/min/mg protein). Uptake was inhibited by both purine and pyrimidine nucleosides but not by nucleobases. [3H]thymidine uptake was sodium and energy independent but was inhibited by nitrobenzylthioinosine at nanomolar concentrations. Adenine uptake by SIRC consisted of a saturable component (K(m) = 14.4 +/- 2.3 microM, V(max) = 0.4 +/- 0.04 nmol/min/mg protein) and a nonsaturable component. Uptake of adenine was inhibited by purine nucleobases but not by the nucleosides or pyrimidine nucleobases and was independent of sodium, energy, and nitrobenzylthioinosine. [3H]ganciclovir uptake involved a carrier-mediated component and was inhibited by the purine nucleobases but not by the nucleosides or pyrimidine nucleobases. However, transport of [3H]adenine across the isolated rabbit cornea was not inhibited by unlabeled adenine. Further, corneal permeability of ganciclovir across a 100-fold concentration range remained constant, indicating that ganciclovir permeates the cornea primarily by passive diffusion. Nucleoside and nucleobase transporters on rabbit cornea and corneal epithelial cell line, SIRC, are functionally different, undermining the utility of the SIRC cell line as an in vitro screening tool for elucidating the corneal permeation mechanism of nucleoside analogs.
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