PMC:2678986 / 23745-26126
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/2678986","sourcedb":"PMC","sourceid":"2678986","source_url":"https://www.ncbi.nlm.nih.gov/pmc/2678986","text":"4.2.2 OATs\nThis family of transporters comprise OAT1, OAT2, OAT3, OAT4 and RST. UST1, UST3 and OAT5 are also considered as transporters of organic anions, however this has not yet been proven (Anzai et al., 2006). The recently identified urate transporter, URAT1 is very similar to RST in terms of amino acid sequence and tissue distribution. Additionally, URAT1 appears to be the human ortholog of murine RST and rat OAT1 (Eraly et al., 2004). Many drugs exist as organic anions at physiological pH levels and therefore OATs present must have a pivotal role in handling these compounds. Studies using Xenopus laevis oocytes showed that antiretroviral nucleoside drugs are substrates for OAT proteins despite the fact that they are not conventional organic anions (Strazielle et al., 2003).\nOat3 is present in the rat brain capillaries (Ohtsuki et al., 2002). There is no direct evidence for the expression of Oat1 at the BBB, however, it is suggested that the observed efflux of certain substances known to be Oat1 substrates from brain to blood indicates that the presence of Oat1 is likely (Sun et al., 2003). ddC and AZT are thought to be removed from the brain by a member of the OAT family (Takasawa et al., 1997; Gibbs and Thomas, 2002; Strazielle et al., 2003). OAT1 and 3 are expressed in the human, murine and rat choroid plexus (Sweet et al., 2002; Alebouyeh et al., 2003) and seem to be largely important in determining the availability of organic anions in the CSF (Eraly et al., 2004). These isoforms are likely candidates for the uptake of CSF-borne AZT and ddC (Gibbs and Thomas, 2002; Strazielle et al., 2003). However, the efflux of AZT was inhibited by specific inhibitors of both of these transporters, which makes it difficult to attribute a particular isoform to this effect.\nAnthonypillai et al. (2006) investigated the distribution of a prodrug of the NRTI tenofovir, known as PMPA to the brain, CSF and choroid plexus. Interestingly, the entry of this pro-drug into the brain was negligible, but it could reach the CSF. The presence of a transporter at the level of the choroid plexus was indicated. Since hOAT1 and hOAT3 are high- and low-affinity transporters of PMPA, respectively (Cihlar et al., 2001; Izzedine et al., 2005), the involvement of these carriers was speculated however no detectable interaction was observed (Anthonypillai et al., 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