Quantitative distribution of mRNAs encoding the 19 human UDP-glucuronosyltransferase enzymes in 26 adult and 3 fetal tissues

被引:179
作者
Court, Michael H. [1 ]
Zhang, Xiuling [2 ]
Ding, Xinxin [2 ]
Yee, Karen K. [3 ]
Hesse, Leah M. [1 ]
Finel, Moshe [4 ]
机构
[1] Tufts Univ, Sch Med, Dept Mol Physiol & Pharmacol, Comparat & Mol Pharmacogen Lab, Boston, MA 02111 USA
[2] New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA
[3] Monell Chem Senses Ctr, Philadelphia, PA 19104 USA
[4] Univ Helsinki, Ctr Drug Res, Fac Pharm, Helsinki, Finland
关键词
UDP-glucuronosyltransferase; glucuronidation; UGT; HEPATIC DRUG GLUCURONIDATION; HUMAN-LIVER-MICROSOMES; FUNCTIONAL-CHARACTERIZATION; AMNIOTIC-FLUID; BILE-ACIDS; PHASE-I; EXPRESSION; POLYMORPHISM; HEPATOCYTES; SPECIFICITY;
D O I
10.3109/00498254.2011.618954
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1. The purpose of this study was to generate, by real-time PCR, a quantitative expression level profile of the 19 human UDP-glucuronosyltransferases (UGTs) of subfamilies 1A, 2A and 2B, in 26 adult and 3 fetal tissues, for better understanding of their roles in xenobiotic and endobiotic metabolism. 2. Adult liver contained the highest level of combined UGTs mRNA, and UGT2B4 was the most abundant isoform in this tissue (40% of total). Other well expressed hepatic UGTs, in decreasing order of mRNA level, were 1A9, 2B7, 1A4, 2B10, 1A1, 1A6, 2B11, 2B15, 1A3, 2A3, 2B17 and 2B28. 3. UGT2B4 was by far the most abundant isoform in the fetal liver (90% of total). 4. The combined UGT mRNA expression in both adult and fetal olfactory epithelium was high, about 20% the adult hepatic level. Interestingly, a large developmental change was found in this tissue from high UGT2A1 and UGT2A2 expression in the fetus to UGT1A6 in the adult. 5. The most abundantly expressed UGTs in the small intestine were 2A3, 1A10, 1A1, 1A6 and 2B7, while 1A10 and 2A3 predominated in the colon. 6. The results provide the most comprehensive data to date on the tissue distribution of the human UGTs.
引用
收藏
页码:266 / 277
页数:12
相关论文
共 38 条
  • [1] FXR induces the UGT2B4 enzyme in hepatocytes: A potential mechanism of negative feedback control of FXR activity
    Barbier, O
    Torra, IP
    Sirvent, A
    Claudel, T
    Blanquart, C
    Duran-Sandoval, D
    Kuipers, F
    Kosykh, V
    Fruchart, JC
    Staels, B
    [J]. GASTROENTEROLOGY, 2003, 124 (07) : 1926 - 1940
  • [2] COUGHTRIE MWH, 1988, MOL PHARMACOL, V34, P729
  • [3] Serum C24 bile acids in the developing human fetus
    Courillon, F
    Gerhardt, MF
    Myara, A
    Daffos, F
    Forestier, F
    Trivin, F
    [J]. BIOLOGY OF THE NEONATE, 1998, 73 (02): : 76 - 88
  • [4] Isoform-selective probe substrates for in vitro studies of human UDP-glucuronosyltransferases
    Court, MH
    [J]. PHASE II CONJUGATION ENZYMES AND TRANSPORT SYSTEMS, 2005, 400 : 104 - 116
  • [5] Evaluation of 3′-azido-3′-deoxythymidine, morphine, and codeine as probe substrates for UDP-glucuronosyltransferase 2B7 (UGT2B7) in human liver microsomes:: Specificity and influence of the UGT2B7*2 polymorphism
    Court, MH
    Krishnaswamy, S
    Hao, Q
    Duan, SX
    Patten, CJ
    Von Moltke, LL
    Greenblatt, DJ
    [J]. DRUG METABOLISM AND DISPOSITION, 2003, 31 (09) : 1125 - 1133
  • [6] Novel polymorphic human UDP-glucuronosyltransferase 2A3: Cloning, functional characterization of enzyme variants, comparative tissue expression, and gene induction
    Court, Michael H.
    Hazarika, Suwagmani
    Krishnaswamy, Soundararajan
    Finel, Moshe
    Williams, J. Andrew
    [J]. MOLECULAR PHARMACOLOGY, 2008, 74 (03) : 744 - 754
  • [7] Interindividual variability in hepatic drug glucuronidation: studies into the role of age, sex, enzyme inducers, and genetic polymorphism using the human liver bank as a model system
    Court, Michael H.
    [J]. DRUG METABOLISM REVIEWS, 2010, 42 (01) : 209 - 224
  • [8] UGT genomic diversity: beyond gene duplication
    Guillemette, Chantal
    Levesque, Eric
    Harvey, Mario
    Bellemare, Judith
    Menard, Vincent
    [J]. DRUG METABOLISM REVIEWS, 2010, 42 (01) : 24 - 44
  • [9] Dopamine Is a Low-Affinity and High-Specificity Substrate for the Human UDP-Glucuronosyltransferase 1A10
    Itaaho, Katriina
    Court, Michael H.
    Uutela, Paivi
    Kostiainen, Risto
    Radominska-Pandya, Anna
    Finel, Moshe
    [J]. DRUG METABOLISM AND DISPOSITION, 2009, 37 (04) : 768 - 775
  • [10] Quantitative Analysis of UDP-Glucuronosyltransferase (UGT) 1A and UGT2B Expression Levels in Human Livers
    Izukawa, Takeshi
    Nakajima, Miki
    Fujiwara, Ryoichi
    Yamanaka, Hiroyuki
    Fukami, Tatsuki
    Takamiya, Masataka
    Aoki, Yasuhiro
    Ikushiro, Shin-ichi
    Sakaki, Toshiyuki
    Yokoi, Tsuyoshi
    [J]. DRUG METABOLISM AND DISPOSITION, 2009, 37 (08) : 1759 - 1768