PMID- 10222050 OWN - NLM STAT- MEDLINE DCOM- 19990607 LR - 20161124 IS - 0003-9861 (Print) IS - 0003-9861 (Linking) VI - 365 IP - 1 DP - 1999 May 1 TI - Expression of UDP-glucuronosyltransferases (UGTs) 2B7 and 1A6 in the human brain and identification of 5-hydroxytryptamine as a substrate. PG - 156-62 AB - The extrahepatic expression of UDP-glucuronosyltransferases (UGTs) is important in the detoxification of a number of endogenous and exogenous compounds, including 5-hydroxytryptamine and morphine. Studies were designed to investigate the extrahepatic expression of human UGTs using RT-PCR techniques and to determine the UGTs involved in the glucuronidation of 5-hydroxytryptamine. Human UGT2B7 expression was found in the human liver, kidney, pancreas, and brain, while UGT1A6 expression is found in the liver, kidney, and brain. This is the first observation of UGTs present in the human central nervous system. Using glucuronidation assays, a significant amount of 5-hydroxytryptamine 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-glucuronide in situ. UGT1A6 could play an important role in the glucuronidation of 5-hydroxytryptamine in vivo, therefore terminating the actions of the neurotransmitter. CI - Copyright 1999 Academic Press. FAU - King, C D AU - King CD AD - Department of Pharmacology, College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA. FAU - Rios, G R AU - Rios GR FAU - Assouline, J A AU - Assouline JA FAU - Tephly, T R AU - Tephly TR LA - eng GR - GM26221/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Arch Biochem Biophys JT - Archives of biochemistry and biophysics JID - 0372430 RN - 0 (DNA Primers) RN - 0 (Morphine Derivatives) RN - 0 (RNA, Messenger) RN - 333DO1RDJY (Serotonin) RN - 64Y9KYM60R (morphine-6-glucuronide) RN - 76I7G6D29C (Morphine) RN - EC 2.4.1.- (UDP-glucuronosyltransferase, UGT1A6) RN - EC 2.4.1.17 (Glucuronosyltransferase) SB - IM MH - Adult MH - Analgesia MH - Brain/*enzymology MH - DNA Primers MH - Fetus MH - Glucuronosyltransferase/genetics/isolation & purification/*metabolism MH - Humans MH - Inactivation, Metabolic MH - Morphine/*metabolism/pharmacology MH - Morphine Derivatives/metabolism MH - RNA, Messenger/isolation & purification MH - Reverse Transcriptase Polymerase Chain Reaction MH - Serotonin/*metabolism MH - Substrate Specificity MH - Tissue Distribution EDAT- 1999/05/01 00:00 MHDA- 1999/05/01 00:01 CRDT- 1999/05/01 00:00 PHST- 1999/05/01 00:00 [pubmed] PHST- 1999/05/01 00:01 [medline] PHST- 1999/05/01 00:00 [entrez] AID - S0003-9861(99)91155-4 [pii] AID - 10.1006/abbi.1999.1155 [doi] PST - ppublish SO - Arch Biochem Biophys. 1999 May 1;365(1):156-62. doi: 10.1006/abbi.1999.1155.