[Molecular identification of the multispecific organic anion transporter family (the OAT family): the role in the pharmacokinetics and toxicokinetics].
The multispecific organic anion transporters have been indicated to be involved in the transmembrane transport of various anionic substances. The kidney and liver possess the distinct organic anion transport pathways for the elimination of potentially toxic anionic drugs and metabolites. In the kidney, proximal tubular cells actively excrete organic anions of both endogenous and exogenous origin. We have isolated the renal multispecific organic anion transporter, OAT1 (organic anion transporter 1), from the rat kidney. OAT1 is a 551-amino acid residue protein with 12 putative membrane spanning domains. OAT1 mediates sodium-independent, anion exchange for a variety of organic anions including p-aminohippurate, cyclic nucleotides, prostanoides, dicarboxylates, and anionic drugs including beta-lactams, non-steroidal antiinflammatory drugs, diuretics and antiviral drugs. So far, three other isoforms have been identified. OATs comprise a new family of multispecific organic anion transporter, i.e., the OAT family. OATs show weak structural similarity to organic cation transporters (OCTs) and OCTN/carnitine transporters. All of the members of the OAT family are commonly expressed in the kidney, suggesting its significance in the renal organic anion excretion. In addition, OAT members appear to be responsible for the distribution/elimination of water soluble anionic drugs into/from the liver, brain and fetus.
Sekine
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Department of Pharmacology and Toxicology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan. sekinet-tky@umin.ac.jp
D000595:Amino Acid Sequence; D000818:Animals; D027321:Anion Transport Proteins; D002352:Carrier Proteins / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008969:Molecular Sequence Data; D010599:Pharmacokinetics; D051381:Rats
D027321:Anion Transport Proteins; D002352:Carrier Proteins