Tissue mRNA expression of the rat UDP-glucuronosyltransferase gene family.

Abstract

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.