Investigation of the activity and regulation of BSEP in different species

Abstract

Event Abstract Back to Event Investigation of the activity and regulation of BSEP in different species Laszlo Vereczkey1* 1 Hungarian Academy of Sciences, Department of Biochemical Pharmacology, Hungary Bile production of liver cells is one of their key functions. Bile salts are necessary for the absorption of lipids. Bile acids are excreted into the biliary canaliculi by active mechanism, by bile salt export pump (BSEP/Bsep), are absorbed in the intestines and taken up by the liver cells, by the sodium-taurocholate-cotransporter (NTCP/Ntcp). The accumulation of bile salts in the liver cells leads to cholestasis, to severe damage or to the death of the hepatocytes. Cholestasis may be the result of genetic mutation of BSEP/Bsep or of its inhibition by different xenobiotics, mainly by drugs. Many drugs that are safe on the base of the preclinical toxicology studies proved to be cholestatic in humans. Our in vitro studies have shown that this controversy may result from the different specificity of human and rat BSEP/Bsep and NTCP/Ntcp. In human hepatocytes BSEP is the predominant efflux pump, whereas in rat hepatocytes about two thirds of bile salts are transported into the blood capillaries. The inhibition of BSEP/Bsep by different drugs leads to the marked accumulation of taurocholate in human hepatocytes, whereas in rat hepatocytes this accumulation is much less due to the compensatory activity of transporters at the basolateral membrane. On the other hand there is sometimes a marked difference in the rate of uptake of drugs inhibiting BSEP/Bsep by the rat and human liver cells, thus protecting the cells from the harmful effect of BSEP/Bsep inhibition, i.e. from cholestasis. Keywords: Bile acids, Cholestasis, hepatocytes BSEP 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: Vereczkey L (2010). Investigation of the activity and regulation of BSEP in different species. Front. Pharmacol. Conference Abstract: 8th Southeast European Congress on Xenobiotic Metabolism and Toxicity - XEMET 2010. doi: 10.3389/conf.fphar.2010.60.00212 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: 05 Mar 2011; Published Online: 04 Nov 2010. * Correspondence: Dr. Laszlo Vereczkey, Hungarian Academy of Sciences, Department of Biochemical Pharmacology, Budapest, Hungary, vela@chemres.hu 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 Laszlo Vereczkey Google Laszlo Vereczkey Google Scholar Laszlo Vereczkey PubMed Laszlo Vereczkey 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.