Expression of UGT1A subfamily in rat brain.
Expression of UGT1A subfamily in rat brain.
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DOI：
10.1002/bdd.2012
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发表时间：
2016-07
影响因子：
2.1
通讯作者：
Y. Sakakibara;M. Katoh;Kuniyuki Imai;Yuya Kondo;Yuki Asai;S. Ikushiro;M. Nadai
中科院分区：
文献类型：
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作者：
Y. Sakakibara;M. Katoh;Kuniyuki Imai;Yuya Kondo;Yuki Asai;S. Ikushiro;M. Nadai
udp -葡萄糖醛酸糖基转移酶（UGT）是一种催化药物代谢中主要的II期反应的酶。葡萄糖醛酸化主要发生在肝脏，但ugt也在肝外组织中表达，在肝外组织的局部代谢中发挥重要作用。UGT1A异构体催化几种药物、神经递质和神经类固醇的糖醛酸化，对大脑产生药理和生理作用。本研究旨在测定大鼠大脑不同区域（即小脑、额叶皮质、顶叶皮质、梨状皮质、海马、延髓、嗅球、纹状体和丘脑）中UGT1A mRNA的表达水平和糖醛酸化活性。结果发现，所有UGT1A亚型在所有9个区域均有表达，但其表达水平在不同区域之间存在差异。大脑中mRNA水平最高的区域和最低的区域之间的差异在2.1到7.8倍之间。采用霉酚酸、对硝基酚和伞形花酮等UGT底物测定葡萄糖醛酸化活性。在大脑的所有九个区域都检测到葡萄糖醛酸化活性。不同区域的活动水平不同，小脑、延髓和嗅球的活动水平最高。葡萄糖醛酸化率最高的区域和最低的区域之间葡萄糖醛酸化活性的差异在5.3到10.1倍之间。这些结果将有助于我们目前对大脑中药物代谢酶的生理和药代动力学作用的理解。版权所有©2016 John Wiley & Sons， Ltd。
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.