中枢支援防御システムとしての血液脳関門輸送の生理機能

抄録

  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 γ-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-α, 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.