Document Detail


Expression of NR1/NR2B N-methyl-D-aspartate receptors enhances heroin toxicity in HEK293 cells.
MedLine Citation:
PMID:  17105944     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Repeated use of drugs of abuse, namely opiates, has been shown to affect glutamate-releasing neurons. Moreover, blockade of N-methyl-D-aspartate (NMDA) receptors (NMDAR) prevents cell death by apoptosis induced by morphine, a heroin metabolite. Thus, in this article we investigated the involvement of different NMDAR subunits in heroin cytotoxicity. Human embryonic kidney (HEK293) cells, which do not express native NMDAR, were transfected with NR1/NR2A or NR1/NR2B subunits. As a control, cells were transfected with NR1 alone, which does not form functional channels. Incubation with heroin for 24 h induced a dose-dependent decrease in cell viability both in NR1-transfected and nontransfected cells. The loss of membrane integrity induced by heroin was more evident in cells transfected with NR1/NR2B than in cells transfected with NR1 alone or NR1/NR2A. This decrease in cell viability was blocked by MK-801, a selective and noncompetitive antagonist of NMDAR. Nevertheless, no significant changes in intracellular adenosine 5'-triphosphate (ATP) were observed in cells treated with heroin. These data implicate NR2B-composed NMDAR as important mediators of heroin neurotoxicity.
Authors:
António Domingues; Teresa Cunha Oliveira; Mário L N Laço; Tice R A Macedo; Catarina R Oliveira; A Cristina Rego
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Annals of the New York Academy of Sciences     Volume:  1074     ISSN:  0077-8923     ISO Abbreviation:  Ann. N. Y. Acad. Sci.     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-11-19     Completed Date:  2007-01-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7506858     Medline TA:  Ann N Y Acad Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  458-65     Citation Subset:  IM    
Affiliation:
Institute of Biochemistry, Faculty of Medicine and Center for Neuroscience and Cell Biology of Coimbra, University of Coimbra, 3004-504 Coimbra, Portugal.
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MeSH Terms
Descriptor/Qualifier:
Cell Line
Cell Membrane / physiology*
Cell Survival
Heroin / toxicity*
Humans
Receptors, N-Methyl-D-Aspartate / metabolism,  physiology*
Transfection
Chemical
Reg. No./Substance:
0/NR1 NMDA receptor; 0/NR2B NMDA receptor; 0/Receptors, N-Methyl-D-Aspartate; 561-27-3/Heroin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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