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Expression of UDP-glucuronosyltransferase 1A4 in human placenta at term

The placenta contains a large variety of metabolizing enzymes, among them UDP-glucuronosyltransferase (UGT). Several UGT2B isozymes have so far been detected in human placenta, but little is known on placental expression of UGT1A isozymes. The antiepileptic drug lamotrigine (LTG) is a UGT1A4-substra...

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Autores principales: Reimers, Arne, Østby, Lene, Stuen, Ina, Sundby, Eirik
Formato: Texto
Lenguaje:English
Publicado: Springer-Verlag 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3034912/
https://www.ncbi.nlm.nih.gov/pubmed/21302032
http://dx.doi.org/10.1007/s13318-010-0021-x
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author Reimers, Arne
Østby, Lene
Stuen, Ina
Sundby, Eirik
author_facet Reimers, Arne
Østby, Lene
Stuen, Ina
Sundby, Eirik
author_sort Reimers, Arne
collection PubMed
description The placenta contains a large variety of metabolizing enzymes, among them UDP-glucuronosyltransferase (UGT). Several UGT2B isozymes have so far been detected in human placenta, but little is known on placental expression of UGT1A isozymes. The antiepileptic drug lamotrigine (LTG) is a UGT1A4-substrate, and its serum concentration falls by over 50% during pregnancy, leading to impaired seizure control. The placenta may be involved in this. Microsomes from term placentas of 4 LTG-users and 10 healthy control subjects were prepared. Western blot analysis detected UGT1A proteins in all placentas. The presence of UGT1A4 in placenta from LTG users was confirmed with UGT1A4 commercial standard and a specific UGT1A4 primary antibody. Since LTG is primarily metabolized by UGT1A4 and this isozyme is shown to be present in placenta at term, it may be hypothesized that the placenta is involved in the fall of LTG serum concentrations during pregnancy.
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spelling pubmed-30349122011-03-16 Expression of UDP-glucuronosyltransferase 1A4 in human placenta at term Reimers, Arne Østby, Lene Stuen, Ina Sundby, Eirik Eur J Drug Metab Pharmacokinet Original Paper The placenta contains a large variety of metabolizing enzymes, among them UDP-glucuronosyltransferase (UGT). Several UGT2B isozymes have so far been detected in human placenta, but little is known on placental expression of UGT1A isozymes. The antiepileptic drug lamotrigine (LTG) is a UGT1A4-substrate, and its serum concentration falls by over 50% during pregnancy, leading to impaired seizure control. The placenta may be involved in this. Microsomes from term placentas of 4 LTG-users and 10 healthy control subjects were prepared. Western blot analysis detected UGT1A proteins in all placentas. The presence of UGT1A4 in placenta from LTG users was confirmed with UGT1A4 commercial standard and a specific UGT1A4 primary antibody. Since LTG is primarily metabolized by UGT1A4 and this isozyme is shown to be present in placenta at term, it may be hypothesized that the placenta is involved in the fall of LTG serum concentrations during pregnancy. Springer-Verlag 2010-12-30 2011 /pmc/articles/PMC3034912/ /pubmed/21302032 http://dx.doi.org/10.1007/s13318-010-0021-x Text en © The Author(s) 2010 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Original Paper
Reimers, Arne
Østby, Lene
Stuen, Ina
Sundby, Eirik
Expression of UDP-glucuronosyltransferase 1A4 in human placenta at term
title Expression of UDP-glucuronosyltransferase 1A4 in human placenta at term
title_full Expression of UDP-glucuronosyltransferase 1A4 in human placenta at term
title_fullStr Expression of UDP-glucuronosyltransferase 1A4 in human placenta at term
title_full_unstemmed Expression of UDP-glucuronosyltransferase 1A4 in human placenta at term
title_short Expression of UDP-glucuronosyltransferase 1A4 in human placenta at term
title_sort expression of udp-glucuronosyltransferase 1a4 in human placenta at term
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3034912/
https://www.ncbi.nlm.nih.gov/pubmed/21302032
http://dx.doi.org/10.1007/s13318-010-0021-x
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