Organic Anion-Transporting Polypeptides

Abstract

Organic anion transporting polypeptides or OATPs are central transporters in the disposition of drugs and other xenobiotics. In addition, they mediate transport of a wide variety of endogenous substrates. The critical role of OATPs in drug disposition has spurred research both in academia and in the pharmaceutical industry. Translational aspects with clinical questions are the focus in academia, while the pharmaceutical industry tries to define and understand the role these transporters play in pharmacotherapy. The present overview summarizes our knowledge on the interaction of food constituents with OATPs, and on the OATP transport mechanisms. Further, it gives an update on the available information on the structure-function relationship of the OATPs, and finally, covers the transcriptional and posttranscriptional regulation of OATPs.

Quercetin mitigates valinomycin‐induced cellular stress via stress‐induced metabolism and cell uptake

“…The effect of membrane potential on the transport of flavonoids has not yet been reported. Although, it has been reported that membrane transporters such as the organic anion‐transporting polypeptide is highly affected by both pH and membrane potential . Organic anion‐transporting polypeptides are expressed on Caco‐2 cells and have been implicated in the transport of quercetin under a pH gradient .…”

Variability in bioavailability of small molecular tyrosine kinase inhibitors

“…A subfamily of the SLC transporter, the organic anion transporting proteins (OATPs) is expressed in the small intestine in several isoforms [96,97]. The OATP group of transporters provides mediation for ionic agents in their intestinal absorption, which results in a higher uptake rate than would be expected diffusion-wise.…”

Role of (Drug) Transporters in Imaging in Health and Disease

“…With respect to OATPs, the transport mechanism is not known in full detail (Hagenbuch and Stieger, 2013;Stieger and Hagenbuch, 2014), impeding prediction of consequences for diagnostic probes resulting from alterations in OATP-mediated transport. For example, most, if not all, OATPs have more than one substrate binding site, which do not always overlap in substrate specificity (Hagenbuch and Stieger, 2013;Stieger and Hagenbuch, 2014). This may affect not only the binding of diagnostic probes, but puts limits on the prediction of drug interactions with diagnostic probes.…”

“…This may affect not only the binding of diagnostic probes, but puts limits on the prediction of drug interactions with diagnostic probes. Furthermore, endogenous substances or some drugs may stimulate rather than inhibit the transport activity of individual OATPs (Hagenbuch and Stieger, 2013;Stieger and Hagenbuch, 2014). And finally, most OATPs are in a substrate dependent manner stimulated by an acid extracellular pH (Leuthold et al, 2009;Hagenbuch and Stieger, 2013;Stieger and Hagenbuch, 2014).…”

“…OATPs constitute a family of truly multispecific transporters and mediate in addition to bile acids the transport of other endogenous substrates, like steroid metabolites (Hagenbuch and Stieger, 2013) (Stieger and Hagenbuch, 2014), a wide variety of drugs (Hagenbuch and Stieger, 2013;Stieger and Hagenbuch, 2014), and endogenous (e.g., bilirubin and its conjugates) and exogenous liver function markers, such as bromosulfophthalein (BSP) or indocyanine green (ICG) (Stieger et al, 2012;Van Beers et al, 2012). The first OATP cloned was identified by using an expression-cloning approach from rat liver mRNA with the liver function marker BSP as lead substrate (Jacquemin et al, 1994), and this OATP is strongly inhibited by ICG (Kullak-Ublick et al, 1994).…”