The physiological, pharmaceutical and pathological role of Organic Anion transporters (OATs) of the SLC22 Family
The human organic anion transporters (OATs) of the SLC22 gene family are polyspecific transporters, mainly located in kidneys. Selected OATs are expressed also in liver, placenta, and brain.
OATs interact with endogenous metabolic end products such as urate and acidic neurotransmitter metabolites, as well as with a multitude of widely used drugs, including antibiotics, antihypertensives, antivirals, anti-inflammatory drugs, diuretics and uricosurics. Thereby, OATs play an important role in renal and hepatic drug elimination and have an impact on pharmacokinetics.
Since OATs are typically found at boundary epithelia, these transporters play an important role in distribution and excretion of drugs and endogenous substrates like urate. Moreover, OATs can be the site of drug-drug interactions during competition of two or more drugs for the same transporter, and mediate cell damage by transporting cytotoxic compounds.
Driving force and mechanism of drug transport by OATs
OATs do not directly utilize ATP hydrolysis for energizing substrate translocation. Most, if not all, members of the OAT family operate as anion exchangers, i.e., they couple the uptake of an organic anion (OA-) into the cell to the release of another organic anion from the cell.
In kidney proximal tubules, OATs are functionally coupled to Na+-driven mono and dicarboxylate (Dic2+) transporters that establish and maintain the intracellular > extracellular gradients of lactate, nicotinate, and α-ketoglutarate.
Example for biomedical impact
Several studies reported an increase in serum urate level during antihypertensive therapy with low-dose diuretics like torasemide and hydrochlorothiazide. These diuretics are substrates of the OATs and, by counter exchange, cause increased urate absorption, leading to hyperuricemia.