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S Majumdar, AK Mitra; Nucleoside Transport Mechanisms in the Rabbit Corneal Epithelial Cell Line (SIRC) and the Isolated Rabbit Cornea: Role in Antiviral Nucleoside Transport . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3258.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To investigate the expression of nucleoside transporters on the rabbit corneal epithelial cell line (SIRC) and the isolated rabbit cornea, and to delineate their role in the transport of antiviral nucleosides. Methods: Uptake and transport studies were carried out at 34ºC using [3H] thymidine as a model nucleoside. Results: Uptake of thymidine followed saturable kinetics (Vmax = 244.8 ± 16.9 picomoles/min/mg of protein, Km = 695.9 ± 80.4 µmoles). [3H] thymidine uptake, in SIRC, was primarily via the "es" type of sodium independent, equilibrative nucleoside transporter. However, the nucleoside transporter expressed on the isolated rabbit cornea was found to be sodium dependent, insensitive to NBT and probably of the N3 type. The nucleoside analogs azidothymidine, idoxuridine and trifluridine inhibited uptake of [3H] thymidine whereas acyclic nucleosides acyclovir and ganciclovir did not. Idoxuridine inhibited the transport of [3H] thymidine across the isolated rabbit cornea but was not transported by the nucleoside transporter. Acyclovir was not found to inhibit transport of [3H] thymidine. Conclusion: Different subtypes of nucleoside transport systems were found to be expressed on the SIRC and intact rabbit cornea. The nucleoside analogs acyclovir, ganciclovir and idoxuridine were not substrates for these transporters. Future drug design strategies could be designed to target this nucleoside transporter to enhance drug delivery across the cornea following topical administration.
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