Organic anion transporters and organic anion transporting polypeptides

Abstract

Organic anion transporters (OATs) are members of the solutecarrier (SLC) group of transporters and belong to the Major Facilitatorsuperfamily (MFS). According to the Human Genome Organization (HUGO), they areassigned to the SLC22A family, that also includes the Organic CationTransporters (OCTs) and the Organic Carnitine (zwitterion) Transporters (alsoknown as Novel Organic Cation Transporters, OCTNs), with which OATs share manygeneral structural features. OATs are multispecific carriers that transportrather small organic anions, including endogenous compounds, such asp-aminohippurate, prostaglandins, guanine nucleotide-related compounds, cGMP,and steroid conjugates, among others, and also exogenous compounds includingmany antivirals, nonsteroidal anti-inflammatory drugs, statins, diureticagents, antimetabolites, and antibiotics, among others. They have a pivotalrole in the basolateral (Phase 0) uptake of their substrates into epithelialcells of drug-eliminating organs and also in drug reabsorption. In humans, mostOATs are highly expressed in the human liver and kidneys, and at lower levels inthe brain, placenta, testis, and prostate. OATs from the SLC22A family includeOAT1-10 (SLC22A6, SLC22A7, SLC22A8, SLC22A11, SLC22A10, SLC22A20, SLC22A9,SLC22A25, SLC22A27, SLC22A13, in that order) and the urate transporter URAT1(SLC22A12). Whereas prototypical members of the SLC22A family can mediate thebidirectional movement of substrates, most of the OATs generally facilitate theuptake of organic anions into epithelial cells (functioning as influxtransporters) by secondary/tertiary active transport (specifically, by exchangewith dicarboxylates, such as α-ketoglutarate) or monocarboxylates.