title: Expression of UGT1A subfamily in rat brain.
abstract: UDP-glucuronosyltransferase (UGT) is an enzyme that catalyses a major phase II reaction in drug metabolism. Glucuronidation occurs mainly in the liver, but UGTs are also expressed in extrahepatic tissues, where they play an important role in local metabolism. UGT1A isoforms catalyse the glucuronidation of several drugs, neurotransmitters and neurosteroids that exert pharmacological and physiological effects on the brain. The aim of the current study was to determine UGT1A mRNA expression levels and glucuronidation activities in different regions of the rat brain (namely the cerebellum, frontal cortex, parietal cortex, piriform cortex, hippocampus, medulla oblongata, olfactory bulb, striatum and thalamus). It was found that all UGT1A isoforms were expressed in all the nine regions, but their expression levels differed between the regions. The difference between the regions of the brain where the mRNA levels were highest and those where they were lowest ranged between 2.1- to 7.8-fold. Glucuronidation activities were measured using the UGT substrates such as mycophenolic acid, p-nitrophenol and umbelliferone. Glucuronidation activity was detected in all nine regions of the brain. Activity levels differed between the regions, and were highest in the cerebellum, medulla oblongata and olfactory bulb. Differences in glucuronidation activity between regions with the highest rates and those with the lowest rates ranged from 5.3- to 10.1-fold. These results will contribute to our current understanding of the physiological and pharmacokinetic roles of drug-metabolizing enzymes in the brain. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Faculty of Pharmacy, Meijo University, Nagoya, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Sakakibara
authors.affiliation: Faculty of Pharmacy, Meijo University, Nagoya, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Katoh
authors.affiliation: Faculty of Pharmacy, Meijo University, Nagoya, Japan.
authors.forename: Kuniyuki
authors.initials: K
authors.lastname: Imai
authors.affiliation: Faculty of Pharmacy, Meijo University, Nagoya, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Kondo
authors.affiliation: Faculty of Pharmacy, Meijo University, Nagoya, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Asai
authors.affiliation: Faculty of Engineering, Toyama Prefectural University, Toyama, Japan.
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Ikushiro
authors.affiliation: Faculty of Pharmacy, Meijo University, Nagoya, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nadai
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D020719:Glucuronides / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000235:genetics*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009173:Mycophenolic Acid / Q000378:metabolism; D009596:Nitrophenols / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D014468:Umbelliferones / Q000378:metabolism; D000099148:UGT1A1 Enzyme
chemical_list: D020719:Glucuronides; D014453:Glucuronosyltransferase; D009173:Mycophenolic Acid; D009596:Nitrophenols; D012333:RNA, Messenger; D014468:Umbelliferones; C499946:Ugt1a1 protein, rat; D000099148:UGT1A1 Enzyme; C031477:7-hydroxycoumarin; C024836:4-nitrophenol
keywords: UGT1A isoform; glucuronidation; rat brain