Polyspecific organic cation transporters: their functions and interactions with drugs

The body is equipped with broad-specificity transporters for the uptake, elimination and distribution of drugs, environmental toxins and metabolic waste products. The organic cation transporters [OCT1-OCT3 (also known as SLC22A1-SLC22A3)], which are expressed in the small intestine, liver, kidney, heart, placenta, lung and brain, facilitate the diffusion of structurally diverse organic cations including monoamine neuro-transmitters and many drugs. These transporters contain substrate-binding pockets with partially overlapping binding domains for substrates and inhibitors. Recent studies in knockout mice show that OCT1 in the liver is involved in the hepatic uptake of cationic drugs and, therefore, affects their net hepatobiliary excretion. In addition, OCT1 and OCT2 in renal proximal tubules participate in the secretion of cationic drugs from the kidney. The recent identification of polymorphisms in human OCTs enables the identification of patients who have an increased risk of adverse drug reactions. Transport studies with expressed OCTs will help to optimize pharmacokinetic properties during the development of new drugs.