Organic anion-transporting polypeptides OATPs

Organic anion transporters can be divided into three major families organic anion transporters (OATs), organic anion transporting polypeptides (OATPs), and multidrug resistance associated proteins (MRPs) [201]. 

St-Pierre, M. V., etal. Characterization of an organic anion-transporting polypeptide (OATP-B) in human placenta. J. Clin. Endocrinol. Metab. 2002, 87, 1856-1863. 

Pizzagalli F, Hagenbuch B, Bottom-ley KM, Meier PJ. Identification of a new human organic anion transporting polypeptide OATP-F. GenBank Accession No AF260704 2001. 

Campbell, S.D., de Morais, S.M. and Xu, J.J. (2004) Inhibition of human organic anion transporting polypeptide OATP 1B1 as a mechanism of drug-induced hyperbilirubinemia. Chemico-Biological Interactions, 150, 179-187. 

Nozawa, T., Imai, K., Nezu, J., Tsuji, A. and Tamai, I. (2004) Functional characterization of pH-sensitive organic anion transporting polypeptide OATP-B in human. Journal of Pharmacology and Experimental Therapeutics, 308,438—445. 

Figure 14.5 Schematic diagram of the magnetic isolation method for rat retinal vascular endothelial cells (RVEC) (A) and the transcript level of organic anion-transporting polypeptides (Oatps) in RVEC (B). A Endothelial cells (RVEC) EC, Nonendothe-lial cells (Non-RVEC) Non-EC. B Not detected N.D. Data taken from Journal of Neurochemistry, 91, Tomi and Hosoya, Application of magnetically isolated rat retinal vascular endothelial cells for the determination of transporter gene expression levels at the inner blood-retinal barrier. 1244-1248, 2004, with permission from Blackwell Publishing.

D. Kobayashi, T. Nozawa, K. Imai, J. Nezu, A. Tsuji, and I. Tamai. Involvement of human organic anion transporting polypeptide OATP-B (SLC21A9) in pH-dependent transport across intestinal apical membrane. J Pharmacol Exp Ther 306 703-708 (2003). 

Figure 2.1 Hepatocyte basolateral bile acid transporters. Protein-bound bile acids returning in portal blood are taken up by the hepatocyte via the sodium taurocholate co-transporting polypeptide (NTCP) and organic-anion-transporting polypeptide (OATP). In cholestasis bile acids may be returned to blood by the multi-drug-resistance-associated protein 3 (MRP3).

Other mechanisms of interaction have also been reported, such as altered activity of other enzymes within the CYP450 family (14—17). Moreover, GFJ may also inhibit the intestinal P-glycoprotein (P-gp)-mediated efflux transport of drugs such as cyclosporine to increase its oral bioavailability (18-21). GFJ and other fruit juices have recently been shown to be potent in vitro inhibitors of a number of organic anion-transporting polypeptides (OATPs) (22,23). 

Satoh H, Yamashita F, Tsujimoto M, et al. Citrus juices inhibit the function of human organic anion transporting polypeptide OATP-B. Drug Metab Dispos 2005 33(4) 518-253. 

Kim RB. Organic anion-transporting polypeptide (OATP) transporter family and drug disposition. Eur J Clin Invest 2003 33(suppl 2) 1-5. 

Organic Anion Transporting Polypeptide (OATP/SLCO) Family... 

Cheng X, Maher J, Chen C, et al. Tissue distribution and ontogeny of mouse organic anion transporting polypeptides (Oatps). Drug Metab Dispos 2005 33 1062-1073. 

Sai Y, Kaneko Y, Ito S, et al. Predominant contribution of organic anion transporting polypeptide OATP-B (OATP2B1) to apical uptake of estrone-3-sulfate by human intestinal Caco-2 cells. Drug Metab Dispos 2006 34 1423-1431. 

D-Ala-deltorphin-I and -II transverse the blood brain barrier in vivo and in vitro [51]. Recently, D-Ala-deltorphin-II was identified as a transport substrate of organic anion transporting polypeptides (Oatp/OATP), a family of polyspecific membrane transporters, strongly expressed at the rat and human blood brain barrier [52]. Modified analogues of these peptides were synthesized to improve their transit across the blood brain barrier [48,49,53]. Because they resist enzyme degradation and can cross endothelial barriers into the CNS, the deltorphins meet the criteria for peptides with potential for systemic administration. 

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