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Liver failure has been reported to alter expression and activity of P\u2010glycoprotein (P\u2010gp) and multidrug resistance\u2010associated protein 2 (Mrp2) at the blood\u2013brain barrier (BBB). The aim of this study was to investigate whether ammonia is involved in abnormalities of expression and activity of P\u2010gp and Mrp2 at the BBB. Hyperammonemic rats were developed by an intraperitoneal injection of ammonium acetate (NH<jats:sub>4<\/jats:sub>Ac, 4.5\u00a0mmol\/kg). Results showed that Mrp2 function markedly increased in cortex and hippocampus of rats at 6\u00a0h following NH<jats:sub>4<\/jats:sub>Ac administration. Significant increase in function of P\u2010gp was observed in hippocampus of rats. Meanwhile, such alterations were in line with the increase in <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> and protein levels of P\u2010gp and Mrp2. Significant increase in levels of nuclear amount of nuclear factor\u2010\u03baB (NF\u2010\u03baB) p65 was also observed. Primarily cultured rat brain microvessel endothelial cells (<jats:styled-content style=\"fixed-case\">rBMEC<\/jats:styled-content>s) were used for <jats:italic>in vitro<\/jats:italic> study. Data indicated that 24\u00a0h exposure to ammonia significantly increased function and expression of P\u2010gp and Mrp2 in <jats:styled-content style=\"fixed-case\">rBMEC<\/jats:styled-content>s, accompanied with activation of NF\u2010\u03baB. Furthermore, such alterations induced by ammonia were reversed by NF\u2010\u03baB inhibitor. In conclusion, this study demonstrates that hyperammonemia increases the function and expression of P\u2010gp and Mrp2 at the BBB via activating NF\u2010\u03baB pathway.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc12944-fig-0006-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><jats:p>Hyperammonemia, a proverbial main factor responsible for neurocognitive disorder and blood\u2013brain barrier (BBB) dysfunction resulting from liver failure, could increase the expression and activity of P\u2010glycoprotein and multidrug resistance\u2010associated protein 2 (Mrp2) at the BBB both <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>. Furthermore, the NF\u2010\u03baB activation stimulated by hyperammonemia may be the potential mechanism underlying such abnormalities induced by hyperammonemia.<\/jats:p>","DOI":"10.1111\/jnc.12944","type":"journal-article","created":{"date-parts":[[2014,9,9]],"date-time":"2014-09-09T08:13:54Z","timestamp":1410250434000},"page":"791-802","source":"Crossref","is-referenced-by-count":37,"title":["Hyperammonemia enhances the function and expression of P\u2010glycoprotein and Mrp2 at the blood\u2013brain barrier through <scp>NF<\/scp>\u2010\u03baB"],"prefix":"10.1111","volume":"131","author":[{"given":"Ji","family":"Zhang","sequence":"first","affiliation":[{"name":"Center of Drug Metabolism and Pharmacokinetics China Pharmaceutical University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center of Drug Metabolism and Pharmacokinetics China Pharmaceutical University Nanjing 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