Pharmaceutical Research

, Volume 24, Issue 9, pp 1745–1758 | Cite as

Contribution of Carrier-Mediated Transport Systems to the Blood–Brain Barrier as a Supporting and Protecting Interface for the Brain; Importance for CNS Drug Discovery and Development

  • Sumio Ohtsuki
  • Tetsuya TerasakiEmail author
Expert Review


The blood–brain barrier (BBB) forms an interface between the circulating blood and the brain and possesses various carrier-mediated transport systems for small molecules to support and protect CNS function. For example, the blood-to-brain influx transport systems supply nutrients, such as glucose and amino acids. Consequently, xenobiotic drugs recognized by influx transporters are expected to have high permeability across the BBB. On the other hand, efflux transporters, including ATP-binding cassette transporters such as P-glycoprotein located at the luminal membrane of endothelial cells, function as clearance systems for metabolites and neurotoxic compounds produced in the brain. Drugs recognized by these transporters are expected to show low BBB permeability and low distribution to the brain. Despite recent progress, the transport mechanisms at the BBB have not been fully clarified yet, especially in humans. However, an understanding of the human BBB transport system is critical, because species differences mean that it can be difficult to extrapolate data obtained in experimental animals during drug development to humans. Recent progress in methodologies is allowing us to address this issue. Positron emission tomography can be used to evaluate the activity of human BBB transport systems in vivo. Proteomic studies may also provide important insights into human BBB function. Construction of a human BBB transporter atlas would be a most important advance from the viewpoint of CNS drug discovery and drug delivery to the brain.

Key words

blood–brain barrier brain capillary endothelial cells carrier-mediated transport efflux transport influx transport pharmacoproteomics 



This study was supported, in part, by a Grant-in-Aid for Scientific Research (S) and Scientific Research on Priority Areas (17081002) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and a 21st Century Center of Excellence (COE) Program grant from the Japan Society for the Promotion of Science. This study was also supported, in part, by the Industrial Technology Research Grant Program from New Energy and the Industrial Technology Development Organization (NEDO) of Japan.


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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  1. 1.Graduate School of Pharmaceutical SciencesTohoku UniversitySendaiJapan
  2. 2.SORSTJapan Science and Technology AgencyTokyoJapan

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