RT Journal Article
SR Electronic
T1 Expression of UGT1A and UGT2B mRNA in Human Normal Tissues and Various Cell Lines
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1461
OP 1464
DO 10.1124/dmd.108.021428
VO 36
IS 8
A1 Akiko Nakamura
A1 Miki Nakajima
A1 Hiroyuki Yamanaka
A1 Ryoichi Fujiwara
A1 Tsuyoshi Yokoi
YR 2008
UL http://dmd.aspetjournals.org/content/36/8/1461.abstract
AB UDP-glucuronosyltransferases (UGTs) are major phase II drug metabolism enzymes that catalyze the glucuronidation of numerous endogenous and exogenous compounds. UGTs are divided into two families, UGT1 and UGT2, based on evolutionary divergence and homology. Nine UGT1A and seven UGT2B functional isoforms have been identified in humans. Glucuronidation occurs mainly in liver but also in various extrahepatic tissues, possibly affecting the pharmacokinetics. In the present study, we comprehensively determined the expression of all functional UGT1A and UGT2B isoforms in normal human tissues including liver, lung, stomach, small intestine, colon, kidney, bladder, adrenal gland, breast, ovary, uterus, and testis by semiquantitative reverse transcription-polymerase chain reaction. In addition, the expressions of these UGTs mRNA in 15 kinds of human tissue-derived cell lines were also analyzed. Many UGT isoforms were abundantly expressed in the liver, gastrointestinal tract, and kidney, supporting previous studies. Interestingly, we found that all UGTs except UGT2B17 were expressed in bladder. In steroid-related tissues, UGTs were expressed in tissue- and isoform-specific manners. Expression profiles in human tissue-derived cell lines were not necessarily consistent with those in corresponding normal tissues. Different expression profiles were observed in distinct cell lines derived from the same organ. The information presented here will be helpful for understanding the glucuronidation in various tissues and for choosing appropriate cell lines for in vitro studies. The American Society for Pharmacology and Experimental Therapeutics