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Titolo:
Identification of cyclosporine A and tacrolimus glucuronidation in human liver and the gastrointestinal tract by a differentially expressed UDP-glucuronosyltransferase: UGT2B7
Autore:
Strassburg, CP; Barut, A; Obermayer-Straub, P; Li, Q; Nguyen, N; Tukey, RH; Manns, MP;
Indirizzi:
Hannover Med Sch, Dept Gastroenterol & Hepatol, D-30625 Hannover, Germany Hannover Med Sch Hannover Germany D-30625 tol, D-30625 Hannover, Germany Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA Univ Calif San Diego La Jolla CA USA 92093 iochem, La Jolla, CA 92093 USA Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA Univ Calif San Diego La Jolla CA USA 92093 rmacol, La Jolla, CA 92093 USA
Titolo Testata:
JOURNAL OF HEPATOLOGY
fascicolo: 6, volume: 34, anno: 2001,
pagine: 865 - 872
SICI:
0168-8278(200106)34:6<865:IOCAAT>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
STABLE EXPRESSION; CDNA CLONING; COS-1 CELLS; HUMAN COLON; HUMAN BILE; 1A LOCUS; METABOLISM; BILIRUBIN; PHENOL; UGT1A;
Keywords:
UGT1A; UGT2B; differential expression; glucuronidation; cyclosporine A; tacrolimus; extrahepatic metabolism; first pass metabolism; immunosuppression; transplantation; tissue specificity;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Strassburg, CP Hannover Med Sch, Dept Gastroenterol & Hepatol, Carl Neuberg Str 1, D-30625 Hannover, Germany Hannover Med Sch Carl Neuberg Str 1 Hannover Germany D-30625
Citazione:
C.P. Strassburg et al., "Identification of cyclosporine A and tacrolimus glucuronidation in human liver and the gastrointestinal tract by a differentially expressed UDP-glucuronosyltransferase: UGT2B7", J HEPATOL, 34(6), 2001, pp. 865-872

Abstract

Background/Aims: The oral administration of the major transplant immunosuppressants cyclosporine A and tacrolimus leads to unpredictable drug levels requiring drug monitoring. Hepatic and extrahepatic metabolism of cyclosporine A and tacrolimus by cytochrome P450 proteins has been analyzed but metabolism and inactivation by glucuronidation has not been investigated. Methods: Cyclosporine A and tacrolimus glucuronidation was measured in hepatic and gastrointestinal microsomal protein, and with 11 recombinant hepatic and extrahepatic family 1 and 2 UDP-glucuronosyltransferases. UDP-glucuronosyltransfcrase transcripts were determined by polymerase chain reaction. Results: Significant cyclosporine and tacrolimus glucuronidation activity was present in endoplasmic reticulum from liver, duodenum, jejunum, ileum and colon, but was absent in stomach. Specific cyclosporine A glucuronidation activity was highest in liver and colon, tacrolimus glucuronidation was highest in liver, Analyses using recombinant UDP-glucuronosyltransferases identified UGT2B7 as a human UDP-glucuronosyltransferase with specific activity toward cyclosporine A and tacrolimus. The hepato-gastrointestinal distribution of immunosuppressant glucuronidation activity corresponded to the differential expression pattern of UGT2B7 mRNA. Conclusions: This study provides conclusive evidence of hepatic and extrahepatic immunosuppressant glucuronidation by human UGT2B7 which was identified to be differentially expressed in the human hepatogastrointestinal tract. Hepatic and extrahepatic glucuronidation may influence the therapeutic efficacy of transplant immunosuppressants. (C) 2001 European Association for the Study of the Liver. Published by Elsevier Science B,V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/09/20 alle ore 05:29:38