ABC Drug Transporter at the Blood-brain Barrier: Effects on Drug Metabolism and Drug Response

Overview

Journal Eur Arch Psychiatry Clin Neurosci

Specialties Neurology
Psychiatry

Date 2006 Jun 20

PMID 16783492

Citations 5

Authors

Martin Ebinger

Manfred Uhr

Affiliations

Soon will be listed here.

Abstract

At the blood-brain barrier (BBB) many cellular and dynamic mechanisms influence the cerebral drug metabolism and the drug response. In this review, we focus mainly on the role P-glycoprotein (P-gp) plays at the BBB. This protein is a 170-kDa ATP-dependent drug transport protein, located in the apical membrane of endothelial cells. Utilizing ATP hydrolysis as an energy source, it exports molecules which attempt to pass through the cell membrane from the outside to the inside, protecting cells from toxins and a wide range of substances. We briefly summarize some of the currently available in vivo and in vitro methods to investigate P-gp and its substrates. Hitherto, no chemical characteristic has been discovered that clearly distinguishes substrates from non-substrates of P-gp. We discuss some examples of substrates stressing the diversity of drugs and endogenous substances that relate to P-gp either as a substrate, an inhibitor, an inducer or as a combination of the above. Finally, we discuss genetic polymorphisms of the genes encoding for P-gp and their effects on drug response.

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