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By using morphine as a model aglycone, we demonstrate that multidrug resistance protein 3 (MRP3\/ABCC3), a protein present in the basolateral membrane of polarized cells, transports morphine-3-glucuronide (M3G) and morphine-6-glucuronide\n                    <jats:italic>in vitro<\/jats:italic>\n                    .\n                    <jats:italic>Mrp3<\/jats:italic>\n                    <jats:sup>(-\/-)<\/jats:sup>\n                    mice are unable to excrete M3G from the liver into the bloodstream, the major hepatic elimination route for this drug. This results in increased levels of M3G in liver and bile, a 50-fold reduction in the plasma levels of M3G, and in a major shift in the main disposition route for morphine and M3G, predominantly via the urine in WT mice but via the feces in\n                    <jats:italic>Mrp3<\/jats:italic>\n                    <jats:sup>(-\/-)<\/jats:sup>\n                    mice. The pharamacokinetics of injected morphine-glucuronides are altered as well in the absence of Mrp3, and this results in a decreased antinociceptive potency of injected morphine-6-glucuronide.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0502530102","type":"journal-article","created":{"date-parts":[[2005,5,10]],"date-time":"2005-05-10T22:13:55Z","timestamp":1115763235000},"page":"7274-7279","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":188,"title":["Mice lacking multidrug resistance protein 3 show altered morphine pharmacokinetics and morphine-6-glucuronide antinociception"],"prefix":"10.1073","volume":"102","author":[{"given":"Noam","family":"Zelcer","sequence":"first","affiliation":[{"name":"Division of Molecular Biology and Center of Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands; Department of Pharmacy and Pharmacology, Slotervaart Hospital, 1066 EC, Amsterdam, The Netherlands; Department of Anesthesiology, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands; and Department of Pharmacology, University of Iowa, Iowa City, IA 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koen","family":"van de Wetering","sequence":"additional","affiliation":[{"name":"Division of Molecular Biology and Center of Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands; Department of Pharmacy and Pharmacology, Slotervaart Hospital, 1066 EC, Amsterdam, The Netherlands; Department of Anesthesiology, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands; and Department of Pharmacology, University of Iowa, Iowa City, IA 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Hillebrand","sequence":"additional","affiliation":[{"name":"Division of Molecular Biology and Center of Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands; 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