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Expression of NR1/NR2B N-methyl-D-aspartate receptors enhances heroin toxicity in HEK293 cells.
Ann N Y Acad Sci. 2006 Aug; 1074:458-65.AN

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.

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Authors+Show Affiliations

Domingues A
Institute of Biochemistry, Faculty of Medicine and Center for Neuroscience and Cell Biology of Coimbra, University of Coimbra, 3004-504 Coimbra, Portugal.
Cunha Oliveira T
No affiliation info available
Laço ML
No affiliation info available
Macedo TR
No affiliation info available
Oliveira CR
No affiliation info available
Rego AC
No affiliation info available

MeSH

Cell LineCell MembraneCell SurvivalHeroinHumansReceptors, N-Methyl-D-AspartateTransfection

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17105944

Citation

Domingues, António, et al. "Expression of NR1/NR2B N-methyl-D-aspartate Receptors Enhances Heroin Toxicity in HEK293 Cells." Annals of the New York Academy of Sciences, vol. 1074, 2006, pp. 458-65.
Domingues A, Cunha Oliveira T, Laço ML, et al. Expression of NR1/NR2B N-methyl-D-aspartate receptors enhances heroin toxicity in HEK293 cells. Ann N Y Acad Sci. 2006;1074:458-65.
Domingues, A., Cunha Oliveira, T., Laço, M. L., Macedo, T. R., Oliveira, C. R., & Rego, A. C. (2006). Expression of NR1/NR2B N-methyl-D-aspartate receptors enhances heroin toxicity in HEK293 cells. Annals of the New York Academy of Sciences, 1074, 458-65.
Domingues A, et al. Expression of NR1/NR2B N-methyl-D-aspartate Receptors Enhances Heroin Toxicity in HEK293 Cells. Ann N Y Acad Sci. 2006;1074:458-65. PubMed PMID: 17105944.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Expression of NR1/NR2B N-methyl-D-aspartate receptors enhances heroin toxicity in HEK293 cells. AU - Domingues,António, AU - Cunha Oliveira,Teresa, AU - Laço,Mário L N, AU - Macedo,Tice R A, AU - Oliveira,Catarina R, AU - Rego,A Cristina, PY - 2006/11/16/pubmed PY - 2007/1/11/medline PY - 2006/11/16/entrez SP - 458 EP - 65 JF - Annals of the New York Academy of Sciences JO - Ann N Y Acad Sci VL - 1074 N2 - 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. SN - 0077-8923 UR - https://www.unboundmedicine.com/medline/citation/17105944/Expression_of_NR1/NR2B_N_methyl_D_aspartate_receptors_enhances_heroin_toxicity_in_HEK293_cells_ L2 - https://doi.org/10.1196/annals.1369.046 DB - PRIME DP - Unbound Medicine ER -