OATPs, OATs and OCTs: the organic anion and cation transporters of the SLCO and SLC22A gene superfamilies

Abstract

The human organic anion and cation transporters are classified within two SLC superfamilies. Superfamily SLCO (formerly SLC21A) consists of organic anion transporting polypeptides (OATPs), while the organic anion transporters (OATs) and the organic cation transporters (OCTs) are classified in the SLC22A superfamily. Individual members of each superfamily are expressed in essentially every epithelium throughout the body, where they play a significant role in drug absorption, distribution and elimination. Substrates of OATPs are mainly large hydrophobic organic anions, while OATs transport smaller and more hydrophilic organic anions and OCTs transport organic cations. In addition to endogenous substrates, such as steroids, hormones and neurotransmitters, numerous drugs and other xenobiotics are transported by these proteins, including statins, antivirals, antibiotics and anticancer drugs. Expression of OATPs, OATs and OCTs can be regulated at the protein or transcriptional level and appears to vary within each family by both protein and tissue type. All three superfamilies consist of 12 transmembrane domain proteins that have intracellular termini. Although no crystal structures have yet been determined, combinations of homology modelling and mutation experiments have been used to explore the mechanism of substrate recognition and transport. Several polymorphisms identified in members of these superfamilies have been shown to affect pharmacokinetics of their drug substrates, confirming the importance of these drug transporters for efficient pharmacological therapy. This review, unlike other reviews that focus on a single transporter family, briefly summarizes the current knowledge of all the functionally characterized human organic anion and cation drug uptake transporters of the SLCO and the SLC22A superfamilies. LINKED ARTICLESBJP recently published a themed section on Transporters. To view the papers in this section visit http://dx

N-Monosubstituted Methoxy-oligo(ethylene glycol) Carbamate Ester Prodrugs of Resveratrol

“…One of the most common processes is the insertion of hydroxyl groups by P450 oxidases [4,5]. These hydroxyls are then targeted by conjugative enzymes of Phase II metabolism, in particular sulfotransferases [6,7] and uridine diphosphate-glucuronosyltransferases [8,9], to produce water-soluble, inactivated metabolites which can be re-exported via Organic Anion/Cation Transporters (OATPs) [10] and ATP-Binding Cassette (ABC)/Multi Drug Resistance (MDR) efflux transporters [11][12][13] and eliminated.…”

Cardiotoxicity testing of diglycolic acid using In Vitro and In Vivo models

“…These preliminary findings may suggest the possibility that the heart is vulnerable to the primary or secondary effects of DGA. Furthermore, the possibility of DGA-induced cardiotoxicity is also supported by recent findings that human cardiomyocytes express molecular transporters of organic anions including dicarboxylic acids [11,12]. As a dicarboxylic acid, DGA has the ability to chelate divalent cations [13], which could be a mechanism to behave as a possible toxin.…”

Permeation of Fluorophore-Conjugated Phalloidin into Live Hair Cells of the Inner Ear Is Modulated by P2Y Receptors

“…Organic anion transporter polypeptides mediate sodium-independent transport of a wide diversity of organic compounds, and currently 11 human OATP proteins have been described (Hagenbuch and Meier 2004;Roth et al 2012). Rodent Oatp1b2 and human OATP1B1 and OATP1B3 enable phalloidin uptake into hepatocytes (Fehrenbach et al 2003;Meier-Abt et al 2004;Lu et al 2008).…”

“…We did not discover Oatp1b2 expression in the utricle, which is the transporter that mediates hepatocellular phalloidin uptake. Thirdly, second messenger systems, including PKC, can regulate OATP transport activity (Kock et al 2010;Roth et al 2012). P2Y6 activates a phosphatidylinositol-calcium second messenger system leading to PKC activation (Kim et al 2003).…”

“…The plasma membrane anionic transporters (OATs) and organic anion transporting polypeptides (OATPs) are transmembrane proteins capable of transporting diverse organic compounds Roth et al 2012). Phalloidin permeates hepatocytes through OATPs (Fehrenbach et al 2003;Meier-Abt et al 2004).…”