{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T13:14:58Z","timestamp":1758633298966},"reference-count":39,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2004,7]]},"abstract":"<jats:p>Benzylpenicillin (PCG; 180 \u03bcmol\/kg), a classic \u03b2-lactam antibiotic, was intravenously given to Sprague-Dawley (SD) rats and multidrug resistance-associated protein 2 (Mrp2)-deficient Eisai hyperbilirubinemic rats (EHBR). A percentage of the [<jats:sup>3<\/jats:sup>H]PCG was excreted into the bile of the rats within 60 min (SD rats: 31.7% and EHBR: 4.3%). Remarkably, a transient increase in the bile flow (\u223c2-fold) and a slight increase in the total biliary bilirubin excretion were observed in SD rats but not in the EHBR after PCG administration. This suggests that the biliary excretion of PCG and its choleretic effect are Mrp2-dependent. Positive correlations were observed between the biliary excretion rate of PCG and bile flow ( r<jats:sup>2<\/jats:sup>= 0.768) and more remarkably between the biliary excretion rate of GSH and bile flow ( r<jats:sup>2<\/jats:sup>= 0.968). No ATP-dependent uptake of [<jats:sup>3<\/jats:sup>H]PCG was observed in Mrp2-expressing Sf9 membrane vesicles, whereas other forms of Mrp2-substrate transport were stimulated in the presence of PCG. GSH efflux mediated by human MRP2 expressed in Madin-Darby canine kidney II cells was enhanced in the presence of PCG in a concentration-dependent manner. In conclusion, the choleretic effect of PCG is caused by the stimulation of biliary GSH efflux as well as the concentrative biliary excretion of PCG itself, both of which were Mrp2 dependent.<\/jats:p>","DOI":"10.1152\/ajpgi.00416.2003","type":"journal-article","created":{"date-parts":[[2004,6,11]],"date-time":"2004-06-11T22:43:19Z","timestamp":1086993799000},"page":"G42-G49","source":"Crossref","is-referenced-by-count":30,"title":["Mrp2 is involved in benzylpenicillin-induced choleresis"],"prefix":"10.1152","volume":"287","author":[{"given":"Kousei","family":"Ito","sequence":"first","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, 263-8675, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomokazu","family":"Koresawa","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, 263-8675, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koichi","family":"Nakano","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, 263-8675, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiharu","family":"Horie","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, 263-8675, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.57.4.760"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.1989.256.1.G22"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M303515200"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(93)80403-H"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(94)90084-1"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/92.16.1295"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00054.2003"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1023\/A:1011942310737"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1016\/S0300-483X(01)00459-0"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1042\/bj3480183"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1054\/bjoc.2000.1262"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.16.10046"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.33.11.1970"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1681.2002.03744.x"},{"key":"R15","unstructured":"Huang Land Vore M.Multidrug resistance p-glycoprotein 2 is essential for the biliary excretion of indocyanine green.Drug Metab Dispos29: 634\u2013637, 2001."},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1124\/mol.59.5.1077"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.2001.281.4.G1034"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(02)00906-1"},{"key":"R19","doi-asserted-by":"crossref","unstructured":"Kobayashi K, Sogame Y, Hara H, and Hayashi K.Mechanism of glutathione S-conjugate transport in canalicular and basolateral rat liver plasma membranes.J Biol Chem265: 7737\u20137741, 1990.","DOI":"10.1016\/S0021-9258(19)38990-2"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1053\/gast.1997.v113.pm9352844"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1042\/bj3400585"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00271.2003"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1986.250.2.C319"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2002.33327"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1042\/bj3380393"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-2736(01)00454-0"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510290319"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109081200"},{"key":"R29","unstructured":"Sathirakul K, Suzuki H, Yasuda K, Hanano M, Tagaya O, Horie T, and Sugiyama Y.Kinetic analysis of hepatobiliary transport of organic anions in Eisai hyperbilirubinemic mutant rats.J Pharmacol Exp Ther265: 1301\u20131312, 1993."},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2001.22648"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90380-9"},{"key":"R32","unstructured":"Tamai I, Maekawa T, and Tsuji A.Membrane potential-dependent and carrier-mediated transport of cefpiramide, a cephalosporin antibiotic, in canalicular rat liver plasma membrane vesicles.J Pharmacol Exp Ther253: 537\u2013544, 1990."},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.2922"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(86)90508-3"},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(90)91180-E"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(90)91029-6"},{"key":"R37","unstructured":"Yabuuchi H, Tamai I, Morita K, Kouda T, Miyamoto K, Takeda E, and Tsuji A.Hepatic sinusoidal membrane transport of anionic drugs mediated by anion transporter Npt1.J Pharmacol Exp Ther286: 1391\u20131396, 1998."},{"key":"R38","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.2001.281.1.G85"},{"key":"R39","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M303504200"}],"container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpgi.00416.2003","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T08:03:14Z","timestamp":1624435394000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpgi.00416.2003"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,7]]},"references-count":39,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2004,7]]}},"alternative-id":["10.1152\/ajpgi.00416.2003"],"URL":"https:\/\/doi.org\/10.1152\/ajpgi.00416.2003","relation":{},"ISSN":["0193-1857","1522-1547"],"issn-type":[{"value":"0193-1857","type":"print"},{"value":"1522-1547","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,7]]}}}