Regulation of taurine transporter expression by NO in cultured human retinal pigment epithelial cells

Taurine is actively transported at the retinal pigment epithelial (RPE) api cal membrane in an Na+- and Cl--dependent manner. Diabetes may alter the fu nction of the taurine transporter. Because nitric oxide (NO) is a molecule implicated in the pathogenesis of diabetes, we asked whether NO would alter the activity of the taurine transporter in cultured ARPE-19 cells. The act ivity of the transporter was stimulated in the presence of the NO donor 3-m orpholinosydnonimine. The stimulatory effects of 3-morpholinosydnonimine we re not observed during the initial 16-h treatment; however, stimulation of taurine uptake was elevated dramatically above control values with 20- and 24-h treatments. Kinetic analysis revealed that the stimulation was associa ted with an increase in the maximal velocity of the transporter with no sig nificant change in the substrate affinity. The NO-induced increase in tauri ne uptake was inhibited by actinomycin D and cycloheximide. RT-PCR analysis and nuclear run-on assays provided evidence for upregulation of the transp orter gene. This study provides the first evidence of an increase in taurin e transporter gene expression in human RPE cells cultured under conditions of elevated levels of NO.