NLT, novel liver-specific transporter; PAH, p-aminohippurate transporter; RST, renal-specific transporter.

drug-drug interactions and hepatotoxicity. For example, rifampicin is a potent inhibitor of both OATP transporters and CYP3A4. Thus giving it together with OATP substrates may reduce hepatic first-pass clearance and increase the bioavailability and decrease the efficacy of an intrahepatically active drug like pravastatin.77 On the other hand, induction of OATP gene expression could increase the hepatic uptake and the total body clearance of the substrate. Expression of the rat Slco1a4 gene is induced by phenobarbital and pregnenolone-16a-carbonitrile (PCN), a well-known inducer of CYP3A4, via the PXR nuclear receptor pathway.72

OATPs have also been found at the two brain-blood interfaces. Oatp1a4 and OATP1A2 were found at the luminal and abluminal membranes of the BBB, where they could mediate the efflux of conjugated metabolites and the brain uptake of drugs like digoxin and DPDPE.72 Oatp1a1 and Oatp1a4 are present in the epithelium of the rat choroid plexus, Oatp1a1 at the apical membrane and Oatp1a4 at the basolateral membrane, where they can account for the secretion of GSH and the removal of LTC4 from the CSF and the uptake of thyroid hormones into the brain.

Only a few OATPs (rat Oatp1a1 and OAT-K1/2, human OATP1A2 and OATP4C1) have been found in the kidney, where they could be responsible for the reabsorption of organic anions.76'78 The human proteins OATP2B1, OATP3A1, and OATP4A1 and the rat transporters Oatp2b1 and Oatp4a1 have been found at the trophoblast epithelium between the fetal and maternal circulations. The OATP system may facilitate the transport of bile acids and steroid hormones, which are extensively synthesized by the fetal liver in utero, across the trophoblast epithelium from the fetus to the maternal circulation.79

No Oatp knockout mice have yet been generated, but studies on several disease models, such as cholestatic liver diseases or cholate feeding, have shown downregulation of hepatocellular Oatps. Hence, the loss of basolateral hepatocellular Oatps during cholestasis and massive liver regeneration can explain the impaired transport under these pathological conditions.

Table 5 Current human oligopeptide transporter, SLC15 gene nomenclature and properties

Human gene

Protein name

Common name


Transport mode

Tissue distribution



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