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Title: Expression of NR1/NR2B N-Methyl-d-Aspartate Receptors Enhances Heroin Toxicity in HEK293 Cells
Authors: Domingues, António 
Cunha-Oliveira, Teresa 
Laço, Mário L. N. 
Macedo, Tice 
Oliveira, Catarina R. 
Rego, A. Cristina 
Issue Date: 8-Mar-2012
Serial title, monograph or event: Annals of the New York Academy of Sciences
Volume: 1074
Abstract: 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.
DOI: 10.1196/annals.1369.046
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais

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