Disease relevance of Slc22a8

• We propose that the absence of Roct expression results in an osteopetrosis phenotype in mice [1].
• The "reduced in osteosclerosis" transporter (Roct), which shows decreased expression in the osteosclerosis (oc) mutant mouse, has high homology with rat and human organic anion transporter 3 (OAT3) [2].

High impact information on Slc22a8

• Impaired organic anion transport in kidney and choroid plexus of organic anion transporter 3 (Oat3 (Slc22a8)) knockout mice [3].
• Uptake sensitive to inhibition by bromosulfophthalein or probenecid was observed for taurocholate, estrone sulfate, and para-aminohippurate in renal slices from wild-type mice, whereas in Oat3(-/-) animals transport of these substances was greatly reduced [3].
• Cellular accumulation of fluorescein was reduced by approximately 75% in CP from Oat3(-/-) mice [3].
• These data indicate a key role for Oat3 in systemic detoxification and in control of the organic anion distribution in cerebrospinal fluid [3].
• In addition, OAT3 interacted with sulfated steroid hormones such as estrone-3-sulfate [4].

Biological context of Slc22a8

• These results indicate that the transport properties and tissue distribution of Roct are similar to those of OAT3, suggesting that Roct functions as mouse OAT3 [2].
• Unlike many other slc22 genes, OAT6 is unpaired in the genome, although it is in proximity to the OAT1/OAT3 gene pair [5].
• The substrate specificity of rat Oat3 and human Oat3 has been elucidated; information on mouse Oat3 (mOat3) is less defined [6].

Anatomical context of Slc22a8

• These results suggest that AR is involved in the functional regulation of OAT3 at the BBB, but not at the inner blood-retinal barrier (iBRB), and this regulation is not affected by gender [7].

Associations of Slc22a8 with chemical compounds

• In the kidney, NKT (OAT1), OCT1, and Roct transcripts appeared at midgestation, coinciding with proximal tubule differentiation, and gradually increased during nephron maturation [8].
• In contrast, only a 33% reduction in estrone sulfate uptake was observed in tissue from Oat3-null mice and, surprisingly, no reduction in taurocholate uptake could be detected [9].
• For PAH, FL, and estrone sulfate, all Oat3-mediated transport was Na dependent [9].
• Because organic anion transporters (OATs) facilitate the renal secretion of weak organic acids, we investigated whether the secretion of bioactive tryptophan metabolites is mediated by OAT1 and OAT3, two prominent members of the OAT family [10].
• [(3)H]Benzylpenicillin uptake by Roct was inhibited by OAT3 substrates and inhibitors, and by sulfate or glucuronide conjugates, and compounds involved in bone turnover [2].

References