1: Nippon Yakurigaku Zasshi. 2003 Jul;122(1):55-64.

[Molecular mechanisms of drug influx and efflux transport at the blood-brain
barrier]

[Article in Japanese]

Ohtsuki S, Hori S, Terasaki T.

Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.

The blood-brain barrier (BBB) segregates the circulating blood from interstitial
fluid in the brain and restricts drug permeability into the brain. Recent studies
have revealed that the BBB exhibits not only blood-to-brain influx transport for
the supply of nutrients, but also brain-to-blood efflux transport to excrete
drugs and endogenous compounds. The influx transport system allows drugs to enter
the brain. (L)-DOPA is transported into the brain by the large neutral amino acid
transport system, system L. A cationic mu-opioid peptide analogue enters the
brain by adsorptive-mediated endocytosis. In contrast, efflux transport limits
the distribution of drugs in the brain. The ATP binding cassette transporter B1
(ABCB1) mediates the efflux transport of lipophilic drugs at the BBB by using ATP
energy. Furthermore, organic anion transporter 3 (OAT3) is expressed at the BBB
and mediates the efflux transport of homovanillic acid, a dopamine metabolite.
This efflux transport is also likely to be involved in the transport of anionic
drugs such as 6-mercaptopurine and acyclovir. Clarifying the BBB transport could
give us important information allowing the development of better CNS drugs and
improving our understanding of the relationship between CNS diseases and BBB
functions.

Publication Types:
English Abstract
Review

PMID: 12843573 [Pubmed - indexed for MEDLINE]