In vitro study reveals liver-specific expression and statin transport by human OATP2, indicating a primary mechanism for hepatic drug clearance.
Key Points
Identify and characterize the tissue distribution, substrate specificity, and sequence identity of the novel human liver transporter OATP2.
Cloned and sequenced human OATP2 to evaluate sequence homology with existing organic anion transporting polypeptide isoforms.
Assayed tissue distribution to determine liver specificity in comparison to other family members.
Conducted substrate transport assays and cis-inhibition studies with bile acids, steroid hormones, and statins including pravastatin, lovastatin, simvastatin, and atorvastatin.
OATP2 exhibited exclusive expression in human liver tissue and shared only 42% sequence identity with four other known family subtypes.
OATP2 transported taurocholic acid, dehydroepiandrosterone sulfate, thyroid hormone, and pravastatin, while showing no transport activity for digoxin or aldosterone.
Cis-inhibition analyses demonstrated that human OATP2 and rat oatp1 mediate uptake of multiple statins, whereas rat oatp2 and human OATP do not transport pravastatin.