{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T09:47:09Z","timestamp":1791107229043,"version":"4.1.0"},"reference-count":33,"publisher":"Elsevier BV","issue":"10","license":[{"start":{"date-parts":[[2011,5,1]],"date-time":"2011-05-01T00:00:00Z","timestamp":1304208000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"the National Institutes of Health (NIH)","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biochemical Pharmacology"],"published-print":{"date-parts":[[2011,5]]},"DOI":"10.1016\/j.bcp.2011.03.001","type":"journal-article","created":{"date-parts":[[2011,3,11]],"date-time":"2011-03-11T10:55:17Z","timestamp":1299840917000},"page":"1248-1254","source":"Crossref","is-referenced-by-count":50,"title":["Distinct pharmacological properties of morphine metabolites at Gi-protein and \u03b2-arrestin signaling pathways activated by the human \u03bc-opioid receptor"],"prefix":"10.1016","volume":"81","author":[{"given":"Nadine","family":"Fr\u00f6lich","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Dees","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Paetz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin J.","family":"Lohse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viacheslav O.","family":"Nikolaev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meinhart H.","family":"Zenk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"Suppl. 1","key":"10.1016\/j.bcp.2011.03.001_bib0005","doi-asserted-by":"crossref","first-page":"S153","DOI":"10.1038\/sj.bjp.0706435","article-title":"75 years of opioid research: the exciting but vain quest for the Holy Grail","volume":"147","author":"Corbett","year":"2006","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.bcp.2011.03.001_bib0010","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1093\/bja\/81.1.12","article-title":"Molecular mechanisms of opioid receptor signal transduction","volume":"81","author":"Jordan","year":"1998","journal-title":"Br J Anaesth"},{"key":"10.1016\/j.bcp.2011.03.001_bib0015","doi-asserted-by":"crossref","first-page":"3322","DOI":"10.1523\/JNEUROSCI.4749-08.2009","article-title":"Two distinct mechanisms mediate acute mu-opioid receptor desensitization in native neurons","volume":"29","author":"Dang","year":"2009","journal-title":"J Neurosci"},{"key":"10.1016\/j.bcp.2011.03.001_bib0020","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1126\/science.1109237","article-title":"Transduction of receptor signals by beta-arrestins","volume":"308","author":"Lefkowitz","year":"2005","journal-title":"Science"},{"key":"10.1016\/j.bcp.2011.03.001_bib0025","first-page":"344","article-title":"Morphine pharmacokinetics and metabolism in humans. Enterohepatic cycling and relative contribution of metabolites to active opioid concentrations","volume":"24","author":"Hasselstrom","year":"1993","journal-title":"Clin Pharmacokinet"},{"key":"10.1016\/j.bcp.2011.03.001_bib0030","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/S0025-6196(11)60750-7","article-title":"Opioid metabolism","volume":"84","author":"Smith","year":"2009","journal-title":"Mayo Clin Proc"},{"key":"10.1016\/j.bcp.2011.03.001_bib0035","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1053\/sane.2002.34194","article-title":"Morphine metabolites: clinical implications","volume":"21","author":"Skarke","year":"2002","journal-title":"Semin Anesth Perioperat Med Pain"},{"key":"10.1016\/j.bcp.2011.03.001_bib0040","doi-asserted-by":"crossref","first-page":"E348","DOI":"10.1007\/BF02854905","article-title":"Role of morphine's metabolites in analgesia: concepts and controversies","volume":"8","author":"Wittwer","year":"2006","journal-title":"AAPS J"},{"key":"10.1016\/j.bcp.2011.03.001_bib0045","doi-asserted-by":"crossref","first-page":"16077","DOI":"10.1073\/pnas.2536719100","article-title":"Gi protein activation in intact cells involves subunit rearrangement rather than dissociation","volume":"100","author":"B\u00fcnemann","year":"2003","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.bcp.2011.03.001_bib0050","doi-asserted-by":"crossref","first-page":"27126","DOI":"10.1074\/jbc.M703272200","article-title":"Live cell monitoring of mu-opioid receptor-mediated G-protein activation reveals strong biological activity of close morphine biosynthetic precursors","volume":"282","author":"Nikolaev","year":"2007","journal-title":"J Biol Chem"},{"key":"10.1016\/j.bcp.2011.03.001_bib0055","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.tips.2007.12.002","article-title":"Optical techniques to analyze real-time activation and signaling of G-protein-coupled receptors","volume":"29","author":"Lohse","year":"2008","journal-title":"Trends Pharmacol Sci"},{"key":"10.1016\/j.bcp.2011.03.001_bib0060","doi-asserted-by":"crossref","first-page":"9528","DOI":"10.1074\/jbc.M413078200","article-title":"Beta-arrestin binding to the beta2-adrenergic receptor requires both receptor phosphorylation and receptor activation","volume":"280","author":"Krasel","year":"2005","journal-title":"J Biol Chem"},{"key":"10.1016\/j.bcp.2011.03.001_bib0065","doi-asserted-by":"crossref","first-page":"30355","DOI":"10.1074\/jbc.M110.114900","article-title":"Formation of a ternary complex among NHERF1, beta-arrestin, and parathyroid hormone receptor","volume":"285","author":"Klenk","year":"2010","journal-title":"J Biol Chem"},{"issue":"Suppl. 1","key":"10.1016\/j.bcp.2011.03.001_bib0070","doi-asserted-by":"crossref","first-page":"S125","DOI":"10.1038\/sj.bjp.0707656","article-title":"Kinetics of G-protein-coupled receptor signals in intact cells","volume":"153","author":"Lohse","year":"2008","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.bcp.2011.03.001_bib0075","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S0065-3233(07)74005-6","article-title":"Kinetic analysis of G protein-coupled receptor signaling using fluorescence resonance energy transfer in living cells","volume":"74","author":"Lohse","year":"2007","journal-title":"Adv Protein Chem"},{"key":"10.1016\/j.bcp.2011.03.001_bib0080","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1002\/elan.200302966","article-title":"Voltammetric oxidation of drugs of abuse \u2013 I. Morphine and metabolites","volume":"16","author":"Garrido","year":"2004","journal-title":"Electroanalysis"},{"key":"10.1016\/j.bcp.2011.03.001_bib0085","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/S0022-3565(25)03379-8","article-title":"The enzymatic acetylation of heroin and related morphine derivatives by blood serum","volume":"71","author":"Wright","year":"1941","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1016\/j.bcp.2011.03.001_bib0090","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/0024-3205(72)90003-3","article-title":"Chemical synthesis and analgesic effect of morphine ethereal sulfates","volume":"11","author":"Mori","year":"1972","journal-title":"Life Sci I"},{"key":"10.1016\/j.bcp.2011.03.001_bib0095","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0378-5173(97)00381-5","article-title":"Ester prodrugs of a potent analgesic, morphine-6-sulfate: syntheses, spectroscopic and physicochemical properties","volume":"163","author":"Preechagoon","year":"1998","journal-title":"Int J Pharm"},{"key":"10.1016\/j.bcp.2011.03.001_bib0100","doi-asserted-by":"crossref","first-page":"3130","DOI":"10.1074\/jbc.M006352200","article-title":"A single nucleotide polymorphic mutation in the human mu-opioid receptor severely impairs receptor signaling","volume":"276","author":"Befort","year":"2001","journal-title":"J Biol Chem"},{"key":"10.1016\/j.bcp.2011.03.001_bib0105","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1124\/mol.52.6.983","article-title":"Naloxone activation of mu-opioid receptors mutated at a histidine residue lining the opioid binding cavity","volume":"52","author":"Spivak","year":"1997","journal-title":"Mol Pharmacol"},{"key":"10.1016\/j.bcp.2011.03.001_bib0110","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/S0091-3057(02)00925-5","article-title":"Pharmacokinetic differences of morphine and morphine-glucuronides are reflected in locomotor activity","volume":"73","author":"Handal","year":"2002","journal-title":"Pharmacol Biochem Behav"},{"key":"10.1016\/j.bcp.2011.03.001_bib0115","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S0022-3565(25)20113-6","article-title":"Poor permeability of morphine 3-glucuronide and morphine 6-glucuronide through the blood\u2013brain barrier in the rat","volume":"278","author":"Bickel","year":"1996","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1016\/j.bcp.2011.03.001_bib0120","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1111\/j.1365-2125.1985.tb02675.x","article-title":"Oral morphine in cancer patients: in vivo kinetics and in vitro hepatic glucuronidation","volume":"19","author":"Sawe","year":"1985","journal-title":"Br J Clin Pharmacol"},{"key":"10.1016\/j.bcp.2011.03.001_bib0125","doi-asserted-by":"crossref","first-page":"8495","DOI":"10.1073\/pnas.0503244102","article-title":"How human neuroblastoma cells make morphine","volume":"102","author":"Boettcher","year":"2005","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.bcp.2011.03.001_bib0130","doi-asserted-by":"crossref","first-page":"14091","DOI":"10.1073\/pnas.0405430101","article-title":"Endogenous formation of morphine in human cells","volume":"101","author":"Poeaknapo","year":"2004","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.bcp.2011.03.001_bib0135","doi-asserted-by":"crossref","first-page":"7357","DOI":"10.4049\/jimmunol.175.11.7357","article-title":"Human white blood cells synthesize morphine: CYP2D6 modulation","volume":"175","author":"Zhu","year":"2005","journal-title":"J Immunol"},{"key":"10.1016\/j.bcp.2011.03.001_bib0140","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/0006-8993(89)91184-0","article-title":"The spinal antinociceptive actions of morphine metabolites morphine-6-glucuronide and normorphine in the rat","volume":"482","author":"Sullivan","year":"1989","journal-title":"Brain Res"},{"key":"10.1016\/j.bcp.2011.03.001_bib0145","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/00007691-199101000-00001","article-title":"Clinical pharmacokinetics of morphine","volume":"13","author":"Glare","year":"1991","journal-title":"Ther Drug Monit"},{"key":"10.1016\/j.bcp.2011.03.001_bib0150","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0006-8993(99)01766-7","article-title":"Pharmacological characterization of morphine-6-sulfate and codeine-6-sulfate","volume":"842","author":"Zuckerman","year":"1999","journal-title":"Brain Res"},{"key":"10.1016\/j.bcp.2011.03.001_bib0155","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1002\/jps.2600740804","article-title":"Analgesic potencies of morphine 3- and 6-sulfates after intracerebroventricular administration in mice: relationship to structural characteristics defined by mass spectrometry and nuclear magnetic resonance","volume":"74","author":"Brown","year":"1985","journal-title":"J Pharm Sci"},{"key":"10.1016\/j.bcp.2011.03.001_bib0160","doi-asserted-by":"crossref","first-page":"2165","DOI":"10.1016\/0024-3205(91)90150-A","article-title":"Mu receptor binding of some commonly used opioids and their metabolites","volume":"48","author":"Chen","year":"1991","journal-title":"Life Sci"},{"key":"10.1016\/j.bcp.2011.03.001_bib0165","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1111\/j.1476-5381.1968.tb07055.x","article-title":"The analgesic action of morphine-n-oxide","volume":"34","author":"Fennessy","year":"1968","journal-title":"Br J Pharmacol"}],"container-title":["Biochemical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006295211001456?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006295211001456?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T03:00:41Z","timestamp":1741057241000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0006295211001456"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,5]]},"references-count":33,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2011,5]]}},"alternative-id":["S0006295211001456"],"URL":"https:\/\/doi.org\/10.1016\/j.bcp.2011.03.001","relation":{},"ISSN":["0006-2952"],"issn-type":[{"value":"0006-2952","type":"print"}],"subject":[],"published":{"date-parts":[[2011,5]]}}}