Organic anion-transporting proteins

Cellular defense mechanisms against toxins (A multistep mechanism for elimination of toxic metabolites and xenobiotics. It involves various transport, oxidation, and conjugation steps.) are usually divided into several steps as it is visualized on Fig. 3. Organic anion transporting proteins (OATPs) are responsible for the cellular uptake of endogenous compounds and... 

MDR-ABC Transporters. Figure 3 Detoxification cellular mechanisms. X, toxic compound X-OH, oxidized toxic compound GS-X, conjugated toxic compound OATP, organic anion transporting proteins CYPs, cytochromes GSH, glutathion UDPGIcUA, Uridine 5-diphosphoglucuronic acid PAPs, 3-phosphoadenylylsulfate. 

OAT/oat Organic anion transporter (protein / nucleic acid)... 

Bergwerk AJ, Shi X, Ford AC, Kanai N, Jacquemin E, Burk RD, Bai S, Novikoff PM, Stieger B, Meier PJ, Schuster VL, Wolkoff AW. Immunologic distribution of an organic anion transport protein in rat liver and kidney. Am J Physiol 1996 271 G231-G238. 

Angeletti RH, Novikoff PM, Juwadi SR, Fritschy JM, Meier PJ, Wolkoff AW. The choroids plexus epithelium is the site of the organic anion transport protein in the brain. PNAS 1994 94 283-286. 

The statins, except for fluvastatin, are poorly absorbed from the gastrointestinal tract [19].They are generally hepatoselective. More lipophilic statins diffuse passively into hepatocytes, and more hydrophilic statins are actively taken up by an organic anion transport protein (OATP) [21]. They are more hepatoselective than the lipophilic statins. 

Organic anion transporter protein inhibition (OATP) - transports drugs into hepatocytes... 

OATP SLC21A3 Polyspecific organic anion transport protein... 

Wang, P., Kim, R.B., Chowdhury, J.R. and Wolkoff, A.W. (2003) The human organic anion transport protein SLC21A6 is not sufficient for bilirubin transport. The Journal of Biological Chemistry, 278, 20695-20699. 

Pang, K.S., Wang, P.J., Chung, A., and Wolkoff, A.W. (1998) The modified dipeptide, enalapril, an angiotensinconverting enzyme inhibitor, is transported by the rat liver organic anion transport protein. Hepatology, 28, 1341-1346. 

S. R., Benke, D., Meier, P.J., and Reme, C.E. (2002) Localization of organic anion transport protein 2 in the apical region of rat retinal pigment epithelium. Investigative Ophthalmology eJ Visual Science, 43, 510-514. 

St-Pierre, M. V., et al. (2004). Temporal expression profiles of organic anion transport proteins in placenta and fetal liver of the rat. American Journal of Physiolog. Regulatory, Integrative and Comparative Physiology, 287(3), R1505-R1516. 

Thyroid hormones enter the extrathyroidal tissues by the action of specific transporters the organic anion transport protein (OATP) and the monocarboxylic transporter (MCT8) (Ekins et al. 1994 Friesema et al. 1999, 2005). Within some cells, deiodinating enzymes can remove an iodine atom from the T4 or T3 molecules and thereby modify the sensitivity of a cell to the actions of the thyroid hormones. The cellular actions of the thyroid hormones are mediated by nuclear receptor proteins, which bind to DNA and regulate transcription with at least two types of genes that encode these receptors (Barettino, Ruiz, and Stunnenberg 1994) these also provide a negative feedback action on the hypothalamic-pituitary axis. T4 is sometimes... 

Behave as substrates for the drug efflux of either P-glycoprotein transporter or organic anion transporter protein. ... 

Fexofenadine, the carboxylic acid metabolite of terfenadine, is widely available (Fig. 37.13). It accounts for the antihistaminic properties of terfenadine, which is very rapidly metabolized via CYP3A4-catalyzed processes. Members of the organic anion transporter protein family and the drug efflux transporter P-glycoprotein are involved in the disposition of fexofenadine. Fexofenadine does not have the antiarrhythmic side effects of terfenadine. 

Adapted from Wilke et al (2007). CYP Cytochrome P450, OATP organic anion transporter protein, ABCBl ABC transporter protein, CPT2 carnitine palmitoyltransferase II, PYGM glycogen phos-phorylase, muscle, COQ2 coenzyme Q2... 

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