OATPtransporters

OATP transporters, or organic anion transporting polypeptides, are a family of membrane transport proteins that mediate the uptake of a wide range of endogenous and exogenous organic anions and some cations. They belong to the solute carrier (SLC) superfamily and are encoded by SLCO genes, such as SLCO1B1, SLCO1B3, SLCO1A2, SLCO2B1, SLCO1C1, and SLCO4C1. These transporters function mainly as sodium-independent carriers that facilitate bidirectional exchange across cell membranes, with notable roles in hepatic and intestinal physiology.

In humans, OATPs are expressed in multiple tissues, with high levels in the liver where OATP1B1 and OATP1B3 on the basolateral hepatocyte membrane mediate uptake of many drugs and endogenous compounds. They are also present in the small intestine, kidney, brain, heart, and placenta, contributing to absorption, distribution, and excretion of substrates. OATP2B1 is particularly associated with intestinal absorption, while OATP4C1 is prominent in the kidney.

Substrates covered by the family include bile acids, bilirubin, steroids, thyroid hormones, and a broad array of drugs such as statins, ARBs, antibiotics, anticancer agents, and antivirals. This broad substrate range underpins their importance in drug disposition and physiological homeostasis.

Clinical relevance and regulation: OATP expression and activity are influenced by nuclear receptors and other factors. Genetic polymorphisms in SLCO genes can alter transporter function and pharmacokinetics; for example, SLCO1B1 variants can increase statin exposure and myopathy risk in some individuals. Transporter inhibition by drugs (drug-drug interactions) is another important consideration in pharmacotherapy.