{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T21:31:15Z","timestamp":1792704675898,"version":"4.5.0"},"reference-count":58,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,7,15]],"date-time":"2013-07-15T00:00:00Z","timestamp":1373846400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["MOP56976"],"award-info":[{"award-number":["MOP56976"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2013,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Intracerebral microdialysis was utilized to investigate the effect of P\u2010glycoprotein (a drug efflux transporter) induction at the mouse blood\u2013brain barrier (<jats:styled-content style=\"fixed-case\">BBB<\/jats:styled-content>) on brain extracellular fluid concentrations of quinidine, an established substrate of P\u2010glycoprotein. Induction was achieved by treating male <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\u20101 mice for 3\u00a0days with 5\u00a0mg\/kg\/day dexamethasone (<jats:styled-content style=\"fixed-case\">DEX<\/jats:styled-content>), a ligand of the nuclear receptor, pregnane X receptor, and a P\u2010glycoprotein inducer. Tandem liquid chromatography mass spectrometric method was used to quantify analytes in dialysate, blood and plasma. P\u2010glycoprotein, pregnane X receptor and Cyp3a11 (metabolizing enzyme for quinidine) protein expression in capillaries and brain homogenates was measured by immunoblot analysis. Following quinidine <jats:italic>i.v<\/jats:italic>. administration, the average ratio of unbound quinidine concentrations in brain extracellular fluid (determined from dialysate samples) to plasma at steady state (375\u2013495\u00a0min) or <jats:italic>K<\/jats:italic><jats:sub>p, uu,<\/jats:sub> <jats:styled-content style=\"fixed-case\"><jats:sub>ECF<\/jats:sub><\/jats:styled-content><jats:sub>\/Plasma<\/jats:sub> in the <jats:styled-content style=\"fixed-case\">DEX<\/jats:styled-content>\u2010treated animals was 2.5\u2010fold lower compared with vehicle\u2010treated animals. In <jats:styled-content style=\"fixed-case\">DEX<\/jats:styled-content>\u2010treated animals, P\u2010glycoprotein expression in brain capillaries was 1.5\u2010fold higher compared with vehicle\u2010treated animals while Cyp3a11 expression in brain capillaries was not significantly different between the two groups. These data demonstrate that P\u2010gp induction mediated by <jats:styled-content style=\"fixed-case\">DEX<\/jats:styled-content> at the <jats:styled-content style=\"fixed-case\">BBB<\/jats:styled-content> can significantly reduce quinidine brain extracellular fluid concentrations by decreasing its brain permeability and further suggest that drug\u2013drug interactions as a result of P\u2010gp induction at the <jats:styled-content style=\"fixed-case\">BBB<\/jats:styled-content> are possible.<\/jats:p><jats:p><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\/jnc12344-fig-0009-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><jats:p>Applying microdialysis, distribution of quinidine, a P\u2010gp substrate, in mouse brain extracellular fluid (ECF) was investigated following ligand\u2010mediated P\u2010glycoprotein (P\u2010gp) induction at the blood\u2013brain barrier (BBB). We demonstrated that a PXR agonist (dexamethasone) significantly up\u2010regulated P\u2010gp in brain capillaries and reduced quinidine brain ECF concentrations. Our data suggest that drug\u2013drug interactions as a result of P\u2010gp induction at the BBB are possible.<\/jats:p>","DOI":"10.1111\/jnc.12344","type":"journal-article","created":{"date-parts":[[2013,6,18]],"date-time":"2013-06-18T15:02:45Z","timestamp":1371567765000},"page":"342-352","source":"Crossref","is-referenced-by-count":42,"title":["<i>In vivo<\/i> induction of P\u2010glycoprotein expression at the mouse blood\u2013brain barrier: an intracerebral microdialysis study"],"prefix":"10.1111","volume":"127","author":[{"given":"Gary N. Y.","family":"Chan","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences Leslie Dan Faculty of Pharmacy University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Saldivia","sequence":"additional","affiliation":[{"name":"NoAb BioDiscoveries Inc. Mississauga Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingbo","family":"Yang","sequence":"additional","affiliation":[{"name":"NoAb BioDiscoveries Inc. Mississauga Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrianna","family":"Pang","sequence":"additional","affiliation":[{"name":"NoAb BioDiscoveries Inc. Mississauga Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00e9s","family":"de Lannoy","sequence":"additional","affiliation":[{"name":"NoAb BioDiscoveries Inc. Mississauga Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reina","family":"Bendayan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Leslie Dan Faculty of Pharmacy University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,7,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2008.07.007"},{"key":"e_1_2_9_3_1","first-page":"413","article-title":"Pregnane X receptor up\u2010regulation of P\u2010glycoprotein expression and transport function at the blood\u2010brain barrier","volume":"66","author":"Bauer B.","year":"2004","journal-title":"Mol. Pharmacol."},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.106.023796"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.106.029512"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jemt.10090"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1369\/jhc.5A6870.2006"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00688186"},{"key":"e_1_2_9_9_1","volume-title":"Gordon Research Conference. Barriers of the CNS: Blood\/Brain Interfaces in Health and Disease","author":"Chan G. N. Y.","year":"2010"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2011.07288.x"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/03602530600569828"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270006299091"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq654"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2008.05720.x"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200241100-00001"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(95)01184-X"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1011988024295"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(00)00107-1"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1528-1157.2001.12301.x"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/js970294v"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2009.03.017"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M010173200"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3028"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-7843.2009.00517.x"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.2174\/156802609787521607"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2005.03114.x"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1210\/mend.14.1.0409"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.106.012294"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.111.180398"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.2012.668184"},{"key":"e_1_2_9_31_1","first-page":"574","article-title":"P\u2010glycoprotein mediates the efflux of quinidine across the blood\u2010brain barrier","volume":"283","author":"Kusuhara H.","year":"1997","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_9_32_1","first-page":"204","article-title":"Functional expression of p\u2010glycoprotein in rat brain microglia","volume":"299","author":"Lee G.","year":"2001","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920008783331077"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.108.024125"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.105.009035"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2004.12.005"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00491.2007"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.2133\/dmpk.19.135"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.108.149690"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1080\/00498250310001630215"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02417.x"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(00)00104-6"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.109.031872"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118699"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/mp200129p"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2004.07.011"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2571(96)00021-0"},{"key":"e_1_2_9_48_1","first-page":"991","article-title":"Effect of capillary efflux transport inhibition on the determination of probe recovery during in vivo microdialysis in the brain","volume":"297","author":"Sun H.","year":"2001","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-011-9318-1"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1177\/1087057111414896"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1995.tb01657.x"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.111.184200"},{"key":"e_1_2_9_53_1","first-page":"S\u2010456","article-title":"The effect of LY\u2010335979 on the distribution kinetics of quinidine to the brain: An in vivo microdialysis study in freely\u2010moving rats","volume":"13","author":"Wang Q.","year":"1996","journal-title":"Pharm. Res."},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-012-9366-1"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-013-9314-4"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1080\/03602530701836712"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2009.10.014"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1159\/000185558"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.21898"}],"container-title":["Journal of Neurochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjnc.12344","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjnc.12344","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jnc.12344","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T21:34:42Z","timestamp":1696282482000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jnc.12344"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,7,15]]},"references-count":58,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2013,11]]}},"alternative-id":["10.1111\/jnc.12344"],"URL":"https:\/\/doi.org\/10.1111\/jnc.12344","archive":["Portico"],"relation":{},"ISSN":["0022-3042","1471-4159"],"issn-type":[{"value":"0022-3042","type":"print"},{"value":"1471-4159","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,7,15]]}}}