PMC:2678986 / 30789-32819 JSONTXT

{"project":"2_test","denotations":[{"id":"19176219-12856181-99578370","span":{"begin":334,"end":338},"obj":"12856181"},{"id":"19176219-12856181-99578370","span":{"begin":334,"end":338},"obj":"12856181"},{"id":"19176219-16111480-99578371","span":{"begin":448,"end":452},"obj":"16111480"},{"id":"19176219-16111480-99578371","span":{"begin":448,"end":452},"obj":"16111480"},{"id":"19176219-16111480-99578372","span":{"begin":930,"end":934},"obj":"16111480"},{"id":"19176219-16111480-99578372","span":{"begin":930,"end":934},"obj":"16111480"},{"id":"19176219-11463208-99578373","span":{"begin":1357,"end":1361},"obj":"11463208"},{"id":"19176219-11463208-99578373","span":{"begin":1357,"end":1361},"obj":"11463208"},{"id":"19176219-11602688-99578375","span":{"begin":1469,"end":1473},"obj":"11602688"},{"id":"19176219-11602688-99578375","span":{"begin":1469,"end":1473},"obj":"11602688"},{"id":"19176219-15651758-99578379","span":{"begin":1750,"end":1754},"obj":"15651758"},{"id":"19176219-15651758-99578379","span":{"begin":1750,"end":1754},"obj":"15651758"},{"id":"19176219-18042828-99578380","span":{"begin":2024,"end":2028},"obj":"18042828"},{"id":"19176219-18042828-99578380","span":{"begin":2024,"end":2028},"obj":"18042828"},{"id":"19176219-12856181-3577004","span":{"begin":334,"end":338},"obj":"12856181"},{"id":"19176219-12856181-3577004","span":{"begin":334,"end":338},"obj":"12856181"},{"id":"19176219-16111480-3577005","span":{"begin":448,"end":452},"obj":"16111480"},{"id":"19176219-16111480-3577005","span":{"begin":448,"end":452},"obj":"16111480"},{"id":"19176219-16111480-3577006","span":{"begin":930,"end":934},"obj":"16111480"},{"id":"19176219-16111480-3577006","span":{"begin":930,"end":934},"obj":"16111480"},{"id":"19176219-11463208-3577007","span":{"begin":1382,"end":1386},"obj":"11463208"},{"id":"19176219-11463208-3577007","span":{"begin":1382,"end":1386},"obj":"11463208"},{"id":"19176219-12824785-3577007","span":{"begin":1382,"end":1386},"obj":"12824785"},{"id":"19176219-12824785-3577007","span":{"begin":1382,"end":1386},"obj":"12824785"},{"id":"19176219-11602688-3577008","span":{"begin":1469,"end":1473},"obj":"11602688"},{"id":"19176219-11602688-3577008","span":{"begin":1469,"end":1473},"obj":"11602688"},{"id":"19176219-18042828-3577009","span":{"begin":1750,"end":1754},"obj":"18042828"},{"id":"19176219-18042828-3577009","span":{"begin":1750,"end":1754},"obj":"18042828"},{"id":"19176219-15512777-3577009","span":{"begin":1750,"end":1754},"obj":"15512777"},{"id":"19176219-15512777-3577009","span":{"begin":1750,"end":1754},"obj":"15512777"},{"id":"19176219-14978234-3577009","span":{"begin":1750,"end":1754},"obj":"14978234"},{"id":"19176219-14978234-3577009","span":{"begin":1750,"end":1754},"obj":"14978234"},{"id":"19176219-15651758-3577009","span":{"begin":1750,"end":1754},"obj":"15651758"},{"id":"19176219-15651758-3577009","span":{"begin":1750,"end":1754},"obj":"15651758"},{"id":"19176219-18042828-3577010","span":{"begin":2024,"end":2028},"obj":"18042828"},{"id":"19176219-18042828-3577010","span":{"begin":2024,"end":2028},"obj":"18042828"}],"text":"4.3.2 Concentrative nucleoside transporters (CNTs)\nThere are three subtypes of sodium-dependent CNTs (CNT1–3) in the SLC28 family. CNT1 is a pyrimidine specific transporter whereas CNT2 is a purine-preferring transporter which also has the ability to transport uridine. CNT3 is a broad selective nucleoside transporter (Gray et al., 2004). These transporters have been identified in the liver, intestine, kidney and choroid plexus. Redzic et al. (2005) demonstrated the presence of rENT1, rENT2 and rCNT2 mRNA and protein in primary cultures of rat brain endothelial cells and rat choroid plexus epithelial cells. rCNT3 was present at the transcript level in choroid plexus epithelium. Furthermore, they showed that the concentrative transport of nucleosides was associated exclusively with the membrane that faces brain fluids in situ, suggesting a role of these barriers in extruding nucleosides from the brain (Redzic et al., 2005).\nUsing rat and human tissues, CNT and ENT cDNAs were cloned and their functional characterisation was determined using Xenopus oocytes. This study revealed that CNT1, CNT3 and ENT2 but not CNT2 or ENT1 transported AZT but with a much lower affinity than endogenous nucleosides. In addition, the influx of AZT into the CSF through choroid epithelial cells was found to be unaffected by endogenous nucleosides (Yao et al., 2001; Strazielle et al., 2003). CNT has also been implicated in the transport of ddI across the BBB (Li et al., 2001). However, the role of human CNT1 as a uptake transporter for ddI and stavudine (d4T) has remained controversial, as some researchers have described such a function for hCNT1 whereas others (Minuesa et al., 2008; Chishty et al., 2004; Chang et al., 2004; Cano-Soldado et al., 2004) have argued that hCNT1/2 (and even hENT1) have a low affinity for these drugs due to the absence of the 3′OH group in the ribose ring of the structure of nucleoside analogs. Conversely, hCNT3 appears to be an efficient transporter of AZT, ddC and ddI (Minuesa et al., 2008)."}