title: [Physiological function of blood-brain barrier transporters as the CNS supporting and protecting system].
abstract: The blood-brain barrier (BBB) segregates the circulating blood from interstitial fluid in the brain and restricts drug permeability into the brain. Our latest studies have revealed that the BBB transporters play important physiological roles in maintaining the brain environment. For an energy-storing system, the creatine transporter localized at the brain capillary endothelial cells (BCECs) mediates the supply of creatine from the blood to the brain. The BBB is involved in the brain-to-blood efflux transport of gamma-aminobutyric acid, and GAT2/BGT-1 mediates this transport process. BCECs also express serotonin and norepinephrine transporters. Organic anion transporter 3 (OAT3) and ASCT2 are localized at the abluminal membrane of the BCECs. OAT3 is involved in the brain-to-blood efflux of a dopamine metabolite, a uremic toxin, and thiopurine nucleobase analogues. ASCT2 plays a role in L-isomer-selective aspartic acid efflux transport at the BBB. Dehydroepiandrosterone sulfate and small neutral amino acids undergo brain-to-blood efflux transport mediated by organic anion transporting polypeptide 2 and ATA2, respectively. The BBB transporters are regulated by various factors: ATA2 by osmolarity, taurine transporter by tumor necrosis factor-alpha, and L-cystine/L-glutamic acid exchange transporter by oxidative stress. Clarifying the physiological roles of BBB transport systems should give important information allowing the development of better central nervous system (CNS) drugs and improving our understanding of the relationship between CNS disorders and BBB function.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-ku, Sendai 980-8578, Japan. sohtsuki@mail.pharm.tohoku.ac.jp
authors.forename: Sumio
authors.initials: S
authors.lastname: Ohtsuki
mesh_terms: D026924:Amino Acid Transport System A / Q000502:physiology; D026962:Amino Acid Transport System ASC / Q000502:physiology; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000502:physiology*; D001921:Brain / Q000098:blood supply; D002491:Central Nervous System Agents; D015195:Drug Design; D042783:Endothelial Cells / Q000378:metabolism; D050485:GABA Plasma Membrane Transport Proteins; D006801:Humans; D027381:Liver-Specific Organic Anion Transporter 1 / Q000502:physiology; D026901:Membrane Transport Proteins / Q000378:metabolism / Q000502:physiology*; D015778:Minor Histocompatibility Antigens; D018377:Neurotransmitter Agents / Q000378:metabolism*; D029362:Organic Anion Transporters, Sodium-Independent / Q000502:physiology; D009994:Osmolar Concentration; D018384:Oxidative Stress / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D026924:Amino Acid Transport System A; D026962:Amino Acid Transport System ASC; D000596:Amino Acids; D002491:Central Nervous System Agents; D050485:GABA Plasma Membrane Transport Proteins; D027381:Liver-Specific Organic Anion Transporter 1; D026901:Membrane Transport Proteins; D015778:Minor Histocompatibility Antigens; D018377:Neurotransmitter Agents; D029362:Organic Anion Transporters, Sodium-Independent; C420506:SLC1A5 protein, human; C498797:SLC38A2 protein, human; C493418:SLC6A13 protein, human; D014409:Tumor Necrosis Factor-alpha; C080679:creatine transporter; C114338:organic anion transport protein 3