Pharmacology. The Bridge to the 21st Century. Molecular mechanisms of drug transport.

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  • ENDOU Hitoshi
    Department of Pharmacology and Toxicology, Kyorin University School of Medicine

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  • 薬理学　　２１世紀への架け橋　　薬物輸送の分子機構
  • ヤクブツ ユソウ ノ ブンシ キコウ
  • 薬理学－21世紀への架け橋

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Abstract

Drugs ingested into the body are transported through the plasma membrane several times. Although hydrophobic low molecules may penetrate the cell membrane according to simple diffusion, most drugs need carrier proteins named transporters for their trans-membrane transport. Drug transporters are classified into 5 groups by their difference in molecular structures, substrate specificities and transport mechanisms. The five groups of drug transports are as follows: (1) organic ion transporter superfamily, (2) ATP-dependent transporter superfamily, (3) peptide transporter family, (4) organic anion transporting polypeptide family originated from liver and (5) amino acid-polyamine-choline transporter superfamily. Among the 5 groups, there are seen several common characteristics such as structures having 12-transmembrane spanning domains, multispecifity in substrate recognition, different tissue distribution and functional regulation by phosphorylation. Multiple substrate specificities of drug transporters are tentatively understood by their evolution, in which at earlier stages these molecules might be essential to absorb endogenously necessary nutrients, and thereafter structural homologs like drugs might be recognized by these transporters. Several topics remain to be elucidated such as functional significance of drug transporters in pharmacokinetics including drug/drug interaction, polymorphism of drug transporter genes, and molecular mechanisms of substrate recognition by drug transporters.

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