{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T07:46:06Z","timestamp":1764747966848,"version":"3.46.0"},"reference-count":66,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:00:00Z","timestamp":1741737600000},"content-version":"vor","delay-in-days":39,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biopharm &amp;amp; Drug Disp"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Sulfated steroids such as pregnenolone sulfate (PregS) are important for neuronal development and cognitive functions. Given the hydrophilic sulfate moiety, it is assumed that PregS requires an active transport mechanism to cross the blood\u2013brain barrier (BBB). The human organic anion transporting polypeptide (OATP)2B1 has been previously shown to transport sulfated steroids and is therefore a proposed candidate for the transport of PregS. In this study, we aimed to investigate the role of OATP2B1 in the uptake of PregS in the brain. Tritium\u2010labeled PregS was intravenously administered to humanized (\n                    <jats:italic>SLCO2B1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>+\/+<\/jats:italic>\n                    <\/jats:sup>\n                    ), knockout (\n                    <jats:italic>rSlco2b1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    ), and wildtype (WT) rats. Accumulation of the radiotracer was analyzed in rat brain, liver, small intestine, kidney, heart, and muscle. Moreover, transporter expression in brain microvessels was assessed through targeted proteomics and Western blot analysis. The involvement of hOATP2B1 in PregS transport across the BBB was further studied using a hBMEC\u2010based in vitro BBB model. Our results indicated no significant difference in accumulation of the radiotracer among the different rat genotypes in the brain or in other tissues. In line with what we observed in the rat model, the subsequent in vitro study showed no involvement of hOATP2B1 in the transport of PregS. Taken together, our findings highlight the species\u2010specific differences in transporter expression and suggest that OATP2B1 does not mediate PregS uptake across the BBB.\n                  <\/jats:p>","DOI":"10.1002\/bdd.70002","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T06:25:20Z","timestamp":1741760720000},"page":"33-46","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pregnenolone Sulfate Permeation at the Blood\u2013Brain Barrier is Independent of OATP2B1\u2014In Vivo and In Vitro Insights"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0585-3451","authenticated-orcid":false,"given":"Valerio","family":"Taggi","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences Biopharmacy University of Basel  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anima M.","family":"Sch\u00e4fer","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Biopharmacy University of Basel  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Oswald","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology Rostock University Medical Center  Rostock Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonny Hanna","family":"Kinzi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Biopharmacy University of Basel  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabell","family":"Seibert","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Biopharmacy University of Basel  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alaa","family":"Al\u2010Khatib","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Biopharmacy University of Basel  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henriette E. Meyer zu","family":"Schwabedissen","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Biopharmacy University of Basel  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,3,12]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010024\u201056303\u2010y"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.93.430"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.8b01189"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22073742"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.21315\/mjms2017.24.5.11"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528\u20101167.2005.66604.x"},{"key":"e_1_2_11_8_1","first-page":"1","article-title":"Neurosteroids: Of the Nervous System, by the Nervous System, for the Nervous System","volume":"52","author":"Baulieu E. E.","year":"1997","journal-title":"Recent Progress in Hormone Research"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.121.000781"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.119.086785"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.CAN\u201005\u20101271"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3791\/57698"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2012.07.010"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.59.5.1277"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/00498254.2021.2025281"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756\u2010200211150\u201000014"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.107.015644"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2010.05.033"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216\u2010016\u20109313\u20106"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2020.107554"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2013.07.031"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.00354"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.106.026450"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.106.011411"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules181012012"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.102.046847"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.23575"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.303"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dmpk.2021.100418"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.64.3.610"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.4595"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm300212s"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16205"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.124.001686"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V134848"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.19.13675"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/msb.2008.61"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1080\/13880209.2022.2036767"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00177912"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.110.036863"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471\u20104159.2004.02552.x"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.WCB.0000050062.57184.75"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V134866"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.61.5.982"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248\u2010013\u20109521\u20103"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15102473"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000410"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003\u2010030174"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.14117"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978\u20100\u2010444\u201053630\u20103.00008\u20107"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2008.06.015"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.123.001884"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1055\/a\u20101305\u20103936"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics13060834"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2007.08.022"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004240000297"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024\u20103205(91)90649\u2010v"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1006\/mpat.2000.0406"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14071376"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.16125"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2011.07.007"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13147"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1243985"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1111\/jphp.12994"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0960\u20100760(97)00041\u20101"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.123.043649"}],"container-title":["Biopharmaceutics &amp; Drug Disposition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdd.70002","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T07:42:19Z","timestamp":1764747739000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdd.70002"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2]]},"references-count":66,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1002\/bdd.70002"],"URL":"https:\/\/doi.org\/10.1002\/bdd.70002","archive":["Portico"],"relation":{},"ISSN":["0142-2782","1099-081X"],"issn-type":[{"type":"print","value":"0142-2782"},{"type":"electronic","value":"1099-081X"}],"subject":[],"published":{"date-parts":[[2025,2]]},"assertion":[{"value":"2024-11-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}