Event Abstract Back to Event Drug metabolizing enzymes and transporters at the blood-brain barrier Jaime Kapitulnik1* 1 The Hebrew University of Jerusalem, Department of Pharmacology, Israel The blood–brain barrier (BBB) is a physical and functional barrier that prevents the entrance of many drugs and chemicals into brain cells regardless of their molecular size. Carrier-mediated transport systems in the BBB, that are active in efflux of drugs, include the P-glycoprotein pump (Pgp/MDR1/ABCB1) and non-Pgp multidrug-resistance proteins (MRPs). The human MDR1-Pgp is located at the luminal site of BBB endothelial cells. It is an amphipatic cationic efflux pump, and limits the influx and diffusion of many drugs and chemicals, thus protecting the brain from the toxic effects of high concentrations of these compounds. Very importantly, Pgp handles also the efflux of endogenous compounds, as is the case with bilirubin (BR), a neurotoxic catabolite of heme. Thus, BR–drug competition for the Pgp in the BBB may affect the entrance of both BR and drugs into the brain. Since Pgp is expressed only after birth, newborn infants are very sensitive to this endogenous neurotoxin, which can diffuse into the brain and precipitate in discrete areas such as the basal ganglia (kernicterus). Pgp can have a pronounced influence on the pharmacodynamic effects of drugs in the brain. Many CNS-active drugs are Pgp substrates (e.g., morphine, phenytoin, anti-brain-cancer drugs, anti-HIV agents, etc.), and consequently inhibition of Pgp at the BBB increases the therapeutic effects of these drugs by increasing their concentrations in the brain. However, in vivo drug–drug interactions at the BBB Pgp can also lead to side effects (e.g., for diltiazem and tacrolimus) and even to CNS toxicity. The MRPs are non-Pgp, amphipatic anion efflux pumps that can also transport cations and neutral compounds (co-transported with GSH). Several of the identified members of the MRP family are expressed at the BBB. Several drug metabolizing enzymes, including cytochrome P450, UDP-glucuronosyltransferase and glutathione transferase, were identified in discrete areas of the brain in which they may perform important functions in the synthesis and elimination of compounds vital to the brain. These enzymes may also participate in the elimination of drugs and toxicants, thus offering an additional protective mechanism for the CNS. Drug-drug and drug-endogenous compound interactions, as well as the 'cross-talk' between enzymes and transporters, will be discussed. Keywords: Blood-Brain Barrier, transporters, drug metabolizing enzymes, P-glycoprotein pump (Pgp), multidrug-resistance proteins (MRPs) Conference: 8th Southeast European Congress on Xenobiotic Metabolism and Toxicity - XEMET 2010, Thessaloniki, Greece, 1 Oct - 5 Oct, 2010. Presentation Type: Invited speaker Topic: Drug transport Citation: Kapitulnik J (2010). Drug metabolizing enzymes and transporters at the blood-brain barrier. Front. Pharmacol. Conference Abstract: 8th Southeast European Congress on Xenobiotic Metabolism and Toxicity - XEMET 2010. doi: 10.3389/conf.fphar.2010.60.00135 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 28 Oct 2010; Published Online: 04 Nov 2010. * Correspondence: Dr. Jaime Kapitulnik, The Hebrew University of Jerusalem, Department of Pharmacology, Jerusalem, 91120, Israel, jaimek@savion.huji.ac.il Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Jaime Kapitulnik Google Jaime Kapitulnik Google Scholar Jaime Kapitulnik PubMed Jaime Kapitulnik Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.