Expression of UDP-glucuronosyltransferases (UGTs) 2B7 and 1A6 in the humanbrain and identification of 5-hydroxytryptamine as a substrate

The extrahepatic expression of UDP-glucuronosyltransferases (UGTs) is impor tant in the detoxification of a number of endogenous and exogenous compound s, including 5-hydroxytryptamine and morphine. Studies were designed to inv estigate the extrahepatic expression of human UGTs using RT-PCR techniques and to determine the UGTs involved in the glucuronidation of 4-hydroxytrypt amine Human UGT2B7 expression was found in the human liver, kidney, pancrea s, and brain, while UGT1A6 expression is found in the liver, kidney, and br ain. This is the first observation of UGTs present in the human central ner vous system. Using glucuronidation assays, a significant amount of 5-hydrox ytryptamine glucuronide was found to be catalyzed by UGT1A6. These studies suggest that UGT2B7 may play an important role in the overall contribution of morphine analgesia by serving to generate the potent morphine-6-O-glucur onide in situ. UGT1A6 could play an important role in the glucuronidation o f B-hydroxytryptamine in vivo, therefore terminating the actions of the neu rotransmitter. (C) 1999 Academic Press.