The physiological, pharmaceutical and pathological role of human Organic Anion Transporting Polypeptides (OATPs) of the SLCO Family
OATP transporters are found in the animal kingdom only and are encoded by genes of the solute carrier organic anion transporter (SLCO) superfamily, which in humans includes 11 members. Based on hydropathy analyses, all OATPs contain 12 transmembrane domains, but this has not been proven experimentally for any OATP. The mechanism of substrate transport via OATP transporters is not completely understood, though a recent computational study suggested that OATPs translocate their substrates through a central, positively charged pore in a so-called rocker-switch type of mechanism. OATP-mediated transport is independent of sodium, chloride and potassium gradients, membrane potential and ATP levels.
Driving force and mechanism of drug transport by OATPs
The cellular uptake via OATP transporters is believed to occur by electroneutral exchange, in which the cellular uptake of organic anions is coupled to the efflux of neutralizing anions such as bicarbonate, glutathione or glutathione-S-conjugates. However, the nature of the neutralizing ion remains unknown for human OATPs.