{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:00:45Z","timestamp":1791896445978,"version":"4.3.4"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":8492,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1992,6]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Dubin\u2013Johnson patients, mutant Corriedale sheep and TR<jats:sup>-<\/jats:sup> and EHBR mutant rats have recessively inherited defective bile canalicular secretion of many nonbile acid organic anions. The human and ovine mutants have black livers and lysosomal pigment accumulation. The livers in TR<jats:sup>-<\/jats:sup> and EHBR mutant rats are not black, and sparse lysosomal pigment accumulation is seen. Previously, we postulated that the unidentified pigment in the Dubin\u2013Johnson syndrome results from the accumulation of tyrosine, phenylalanine and tryptophan metabolites, such as metanephrine, which are normally secreted in bile as organic anions. We tested this hypothesis in TR<jats:sup>-<\/jats:sup> rats. H\u2013epinephrine was injected intravenously; control rats secreted 2.80% \u00b1 0.52% of the injected dose in bile as compared with 0.19% \u00b1 0.07% in TR<jats:sup>-<\/jats:sup> rats. From 82% to 90% of biliary radioactivity was due to polar conjugates in control rats and mutant rats. TR<jats:sup>-<\/jats:sup> rats retained more of the injected dose in the liver, particularly in lysosomes, and secreted more in urine than did control rats. After feeding control and TR<jats:sup>-<\/jats:sup> rats for 4 mo with a rat chow diet supplemented with 4% tyrosine, tryptophan and phenylalanine, the liver did not become grossly black; however, histological and electron microscopic study revealed dense lysosomal pigment accumulation in TR<jats:sup>-<\/jats:sup> rats. Intraportal injection of metanephrine resulted in the appearance of black liver in TR<jats:sup>-<\/jats:sup> rats that persisted for at least 2 hr and was not associated with pigment accumulation by light or electron microscopic examination. After mating TR<jats:sup>-<\/jats:sup> males with EHBR females, all 38 offspring had bilirubinuria, which indicates that TR<jats:sup>-<\/jats:sup> and EHBR are allelic mutants. We propose that defective canalicular secretion of anionic metabolites may be responsible for the black lysosomal pigment that accumulates in the Dubin\u2013Johnson syndrome, mutant Corriedale sheep and in TR<jats:sup>-<\/jats:sup> rats that were fed a diet enriched in aromatic amino acids. (Hepatology 1992;15:1154-1159).<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.1840150629","type":"journal-article","created":{"date-parts":[[2007,3,4]],"date-time":"2007-03-04T00:42:06Z","timestamp":1172968926000},"page":"1154-1159","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":56,"title":["Defective Biliary Excretion of Epinephrine Metabolites in Mutant (Tr-) Rats: Relation to the Pathogenesis of Black Liver in the Dubin\u2013Johnson Syndrome and Corriedale Sheep With An Analogous Excretory Defect"],"prefix":"10.1097","volume":"15","author":[{"given":"Tsuneo","family":"Kitamura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Alroy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zenaida","family":"Gatmaitan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayasu","family":"Inoue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Mikami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Jansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irwin M.","family":"Arias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"10.1002\/hep.1840150629-BIB1","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1097\/00005792-195409000-00001","volume":"33","author":"Dubin","year":"1954","journal-title":"Medicine"},{"key":"10.1002\/hep.1840150629-BIB2","doi-asserted-by":"crossref","first-page":"952","DOI":"10.7326\/0003-4819-41-5-952","volume":"41","author":"Sprinz","year":"1954","journal-title":"Ann Intern Med"},{"key":"10.1002\/hep.1840150629-BIB3","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/S0016-5085(19)34312-4","volume":"51","author":"Butt","year":"1966","journal-title":"Gastroenterology"},{"key":"10.1002\/hep.1840150629-BIB4","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1056\/NEJM197301182880301","volume":"288","author":"Wolkoff","year":"1973","journal-title":"N Engl J Med"},{"key":"10.1002\/hep.1840150629-BIB5","first-page":"549","volume":"39","author":"Shani","year":"1970","journal-title":"Q J Med"},{"key":"10.1002\/hep.1840150629-BIB6","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1016\/0002-9343(61)90135-8","volume":"31","author":"Arias","year":"1961","journal-title":"Am J Med"},{"key":"10.1002\/hep.1840150629-BIB7","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/0002-9343(58)90315-2","volume":"24","author":"Dubin","year":"1958","journal-title":"Am J Med"},{"key":"10.1002\/hep.1840150629-BIB8","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/S0016-5085(19)33321-9","volume":"63","author":"Ware","year":"1972","journal-title":"Gastroenterology"},{"key":"10.1002\/hep.1840150629-BIB9","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1007\/BF02233553","volume":"13","author":"Cornelius","year":"1968","journal-title":"Am J Dig Dis"},{"key":"10.1002\/hep.1840150629-BIB10","first-page":"36","volume":"4","author":"Gutstein","year":"1968","journal-title":"Isr J Med Sci"},{"key":"10.1002\/hep.1840150629-BIB11","first-page":"709","volume":"146","author":"Cornelius","year":"1965","journal-title":"J Am Vet Med Assoc"},{"key":"10.1002\/hep.1840150629-BIB12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1172\/JCI105078","volume":"43","author":"Arias","year":"1964","journal-title":"J Clin Invest"},{"key":"10.1002\/hep.1840150629-BIB13","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1085\/jgp.53.2.238","volume":"53","author":"Alpert","year":"1969","journal-title":"J Gen Physiol"},{"key":"10.1002\/hep.1840150629-BIB14","first-page":"65","volume-title":"Sonderdruck aus Ikterus","author":"Arias","year":"1967","unstructured":"Chronic idiopathic jaundice. In: ed. Sonderdruck aus Ikterus. New York: Verlag, 1967: 65\u201371."},{"key":"10.1002\/hep.1840150629-BIB15","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1172\/JCI105250","volume":"44","author":"Arias","year":"1965","journal-title":"J Clin Invest"},{"key":"10.1002\/hep.1840150629-BIB16","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1002\/hep.1840050408","volume":"5","author":"Jansen","year":"1985","journal-title":"Hepatology"},{"key":"10.1002\/hep.1840150629-BIB17","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1002\/hep.1840070116","volume":"7","author":"Jansen","year":"1987","journal-title":"Hepatology"},{"key":"10.1002\/hep.1840150629-BIB18","first-page":"250","volume":"26","author":"Mikami","year":"1986","journal-title":"Cong Anom"},{"key":"10.1002\/hep.1840150629-BIB19","doi-asserted-by":"crossref","first-page":"3557","DOI":"10.1073\/pnas.87.9.3557","volume":"87","author":"Kitamura","year":"1990","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1002\/hep.1840150629-BIB20","author":"Nishida","unstructured":", , . ATP-dependent organic anion transport system in normal and TR\u2013 rat liver canalicular membrane [in press]. 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