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Vol. 31, Issue 3, 326-333, March 2003
Department of Pharmacology, Toxicology, and Therapeutics,
University of Kansas Medical Center, Kansas City, Kansas
UDP-Glucuronosyltransferases (UGTs) are phase II biotransformation
enzymes that glucuronidate numerous endobiotic and xenobiotic substrates. Glucuronidation increases the water solubility of the
substrate and facilitates renal and biliary excretion of the resulting
glucuronide conjugate. UGTs have been divided into two gene families,
UGT1 and UGT2. Tissue distribution of UGTs has not been thoroughly
examined, and such data could provide insight into the importance of
individual UGT isoforms in specific tissues and to the pharmacokinetics
and target organ toxicity of UGT substrates. Therefore, the aim of this
study was to determine mRNA levels of rat UGT1 and UGT2 family members
in liver, kidney, lung, stomach, duodenum, jejunum, ileum, large
intestine, cerebellum, and cerebral cortex, as well as nasal epithelium
for UGT2A1. Tissue levels of UGT mRNA were detected using branched DNA
signal amplification analysis. Three UGT isoforms, UGT1A1, UGT1A6, and
UGT2B12, were detected in many tissues, whereas distribution of other
UGT isoforms was more tissue-specific. For example, UGT2A1 was detected
predominantly in nasal epithelium. Additionally, UGT1A5, UGT2B1,
UGT2B2, UGT2B3, and UGT2B6 were detected primarily in liver.
Furthermore, detection of UGT1A2, UGT1A3, UGT1A7, and UGT2B8 was
somewhat specific to gastrointestinal (GI) tract. However, not all of
these UGTs were detected in all portions of the GI tract. UGT1A8 was
unique in that it was barely detectable in any of the tissues examined. In conclusion, some UGT isoforms were expressed in multiple tissues, whereas other UGT isoforms were predominantly expressed in a certain tissue such as nasal epithelium, liver, or GI tract.
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