Molecular identification of the multispecific organic anion transporter family(The OAT family): The role in the pharmacokinetics and toxicokinetics.

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  • SEKINE Takashi
    Department of Pharmacology and Toxicology, Kyorin University School of Medicine

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  • 多選択性有機アニオントランスポーターファミリー（ＯＡＴ　ｆａｍｉｌｙ）の同定と薬物輸送における役割の解析
  • 受賞者講演 多選択性有機アニオントランスポーターファミリー(OAT family)の同定と薬物輸送における役割の解析
  • ジュショウシャ コウエン タセンタクセイ ユウキ アニオントランスポーターファミリー OAT family ノ ドウテイ ト ヤクブツ ユソウ ニ オケル ヤクワリ ノ カイセキ

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Abstract

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 β-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 solubule anionic drugs into/from the liver, brain and fetus.

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