A novel human hepatic organic anion transporting polypeptide (OATP2). Identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters.

Article Details

Citation

Hsiang B, Zhu Y, Wang Z, Wu Y, Sasseville V, Yang WP, Kirchgessner TG

A novel human hepatic organic anion transporting polypeptide (OATP2). Identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters.

J Biol Chem. 1999 Dec 24;274(52):37161-8.

PubMed ID
10601278 [ View in PubMed
]
Abstract

A novel human organic transporter, OATP2, has been identified that transports taurocholic acid, the adrenal androgen dehydroepiandrosterone sulfate, and thyroid hormone, as well as the hydroxymethylglutaryl-CoA reductase inhibitor, pravastatin. OATP2 is expressed exclusively in liver in contrast to all other known transporter subtypes that are found in both hepatic and nonhepatic tissues. OATP2 is considerably diverged from other family members, sharing only 42% sequence identity with the four other subtypes. Furthermore, unlike other subtypes, OATP2 did not transport digoxin or aldosterone. The rat isoform oatp1 was also shown to transport pravastatin, whereas other members of the OATP family, i.e. rat oatp2, human OATP, and the prostaglandin transporter, did not. Cis-inhibition studies indicate that both OATP2 and roatp1 also transport other statins including lovastatin, simvastatin, and atorvastatin. In summary, OATP2 is a novel organic anion transport protein that has overlapping but not identical substrate specificities with each of the other subtypes and, with its liver-specific expression, represents a functionally distinct OATP isoform. Furthermore, the identification of oatp1 and OATP2 as pravastatin transporters suggests that they are responsible for the hepatic uptake of this liver-specific hydroxymethylglutaryl-CoA reductase inhibitor in rat and man.

DrugBank Data that Cites this Article

Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
AtorvastatinSolute carrier organic anion transporter family member 1A2ProteinHumans
No
Substrate
Details
AtorvastatinSolute carrier organic anion transporter family member 1B1ProteinHumans
No
Substrate
Inhibitor
Details
LovastatinSolute carrier organic anion transporter family member 1A2ProteinHumans
Unknown
Inhibitor
Details
LovastatinSolute carrier organic anion transporter family member 1B1ProteinHumans
Unknown
Substrate
Inhibitor
Details
PravastatinSolute carrier organic anion transporter family member 1A2ProteinHumans
No
Substrate
Details
PravastatinSolute carrier organic anion transporter family member 1B1ProteinHumans
No
Substrate
Details
PravastatinSolute carrier organic anion transporter family member 1B3ProteinHumans
No
Substrate
Details
SimvastatinSolute carrier organic anion transporter family member 1A2ProteinHumans
Unknown
Inhibitor
Details
SimvastatinSolute carrier organic anion transporter family member 1B1ProteinHumans
Unknown
Substrate
Inhibitor
Details
Taurocholic acidSolute carrier organic anion transporter family member 1A2ProteinHumans
Unknown
Substrate
Inhibitor
Inducer
Details
Taurocholic acidSolute carrier organic anion transporter family member 1B1ProteinHumans
Unknown
Substrate
Inhibitor
Inducer
Details
Polypeptides
NameUniProt ID
Solute carrier organic anion transporter family member 1B1Q9Y6L6Details