Organic anion-transporting polypeptide

An organic anion-transporting polypeptide (OATP) is a membrane transport protein or 'transporter' that mediates the transport of mainly organic anions across the cell membrane. Therefore OATPs are present in the lipid bilayer of the cell membrane, acting as the cell's gatekeepers. OATPs belong to the Solute Carrier Family (SLC), more specifically the Solute Carrier Organic Anion (SLCO) gene subfamily

Function
Organic anion transporting polypeptides carry bile acids as well as bilirubin and numerous hormones such as thyroid and steroid hormones across the basolateral membrane (facing sinusoids) in hepatocytes, for excretion in bile. As well as expression in the liver, OATPs are expressed in many other tissues on basolateral and apical membranes, transporting anions, as well as neutral and even cationic compounds. They also transport an extremely diverse range of drug compounds, ranging from anti-cancer, antibiotic, lipid lowering to anti-diabetic drugs, as well as toxins and poisons.

They also transport the dye bromsulphthalein, availing it as a liver-testing substance.

Proteins
The table below shows the 11 known human OATPs. Note: Human OATPs are designated with capital letters, animal Oatps are designated with lower class letters. The 'SLCO' stands for their gene name; 'solute carrier organic anion.' Previous nomenclature using letters and numbers (e.g. OATP-A, OATP-8 is no longer correct. The most well characterised human OATPs are OATP1A2, OATP1B1, OATP1B3 and OATP2B1. Very little is known about the function and characteristics of OATP5A1 and OATP6A1.

Pharmacology
The OATPs play a fundamental role in the transport of drugs across the cell membrane, particularly in the liver and kidney. In the liver, OATPs are expressed on the basolateral membrane of hepatocytes, transporting compounds into the hepatocyte for biotransformation. A number of drug-drug interactions have been associated with the OATPs, affecting the pharmacokinetics and pharmacodynamics of drugs. This is most commonly where one drug inhibits the transport of another drug into the hepatocyte, so that it is retained in the body. The OATPs most associated with these interactions are OATP1B1, OATP1B3 and OATP2B1, which are all present on the hepatocyte basolateral membrane. The most clinically relevant interactions have been associated with the lipid lowering drugs statins, which led to the removal of cerivastatin from the market in 2002. Single nucleotide polymorphisms (SNPs) are also associated with the OATPs; particularly OATP1B1, causing

Probenecid inhibits organic anion transporting polypeptides.

It is likely that along with the Organic Anion Transporters, Organic Cation transporters and the ATP-binding cassette transporters, the OATPs play a central role in the absorption, distribution, metabolism and exretion (ADME) of drug compounds.

Evolution
Oatps are present in many animals, including zebrafish, dog, cow, rat, mouse, monkey and horse. Oatps are not present in bacteria, indicating their evolution from the animal kingdom. However homologs do not correlate well with the human OATPs and therefore it is likely that isoforms arose by gene duplication. An Oatp has however been found in the little skate (Raja erinacea), suggesting that their evolution was early in the formation of the animal kingdom.