, Volume 2, Issue 1, pp 63–72

Brain-to-blood transporters for endogenous substrates and xenobiotics at the blood-brain barrier: An overview of biology and methodology


DOI: 10.1602/neurorx.2.1.63

Cite this article as:
Terasaki, T. & Ohtsuki, S. Neurotherapeutics (2005) 2: 63. doi:10.1602/neurorx.2.1.63


In the past decade, research into P-glycoprotein involving the blood-brain barrier (BBB) has seen a shift in the concept of the BBB as a structural barrier to that of a functional barrier for xenobiotics and changed simultaneously the strategy for the discovery and development of drugs acting in the CNS. As far as making advances in neurotherapeutics are concerned, the brain-to-blood transport function at the BBB will be one of the most important issues. Knowing the limitations of thein vivo andin vitro methods for BBB efflux research, it is essential to adopt a multidisciplinary approach in investigating the true physiological role of the BBB. Among several methods, the Brain Efflux Index method and the use of conditionally immortalized brain capillary endothelial cell lines, established from transgenic rats harboring temperature-sensitive simian virus 40 large T-antigen gene, are likely to be very useful tools for the BBB efflux transport research. According to our recent findings using these methods, several transporters in the brain capillary endothelial cells appear to play an important role in reducing the brain level of hydrophilic endogenous substrates produced either in the brain or peripheral organs, e.g., neurotransmitters, neuromodulators, metabolites of neurotransmitters, and uremic toxins. It has been reported also that large hydrophilic molecules, such as IgG, apo-transferrin, and amyloid-β peptide, are susceptible to brain-to-blood efflux transport. In the light of the latest findings, we have formed the hypothesis that the BBB acts as a CNS detoxifying system for both endogenous substrates and xenobiotics in the brain. A fuller understanding of the physiological role of BBB efflux transporters will provide rational insights to assist in the development of safer neurotherapeutics.

Key Words

Blood-brain barrier efflux transportbrain efflux index methodconditionally immortalized cell lineMDR1ABCG2/BCRPamyloid peptide
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© The American Society for Experimental NeuroTherapeutics, Inc 2005

Authors and Affiliations

  1. 1.New Industry Creation Hatchery Center and Graduate School of Pharmaceutical SciencesTohoku UniversitySendaiJapan
  2. 2.CREST & SORSTJapan Science and Technology AgencyJapan