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Pharmacological properties of acquired excitotoxicity in Chinese hamster ovary cells transfected with N-methyl-D-aspartate receptor subunits.
J Pharmacol Exp Ther. 1996 Nov; 279(2):515-23.JP

Abstract

The cytotoxicity induced by the transient expression of functional N-methyl-D-aspartate (NMDA) receptors has been examined with the use of a luciferase reporter assay in Chinese hamster ovary cells. Various NMDA receptor antagonists, in a dose-dependent manner, prevented a loss of luciferase activity 24 to 48 hr post-transfection of either the NR1/NR2A or NR1/ NR2B subunit receptor configurations, likely correlating to the time required to express functionally these receptors. Both glutamate and NMDA were potently cytotoxic to transfected cells previously protected by antagonists. The novel ifenprodil analog (1S,2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol (CP101,606-27) protected cells expressing NR1/NR2B, but not those cells expressing either NR1/NR2A or, putatively, NR1/NR2A/NR2B. Decreased cytotoxicity was observed when a mutated NR1 subunit (N616R) with reduced Ca++ permeability was used in coexpression studies with NR2A or NR2B. In contrast to our results with NR1/NR2A or NR1/NR2B, cells expressing NR1/NR2C did not perish. Our studies suggest that expression of functional NMDA receptors in non-neuronal cells leads to a form of excitotoxicity similar to that observed in mammalian neurons in vitro.

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Authors+Show Affiliations

Boeckman FA
Department of Neurobiology, University of Pittsburgh School of Medicine, Pennsylvania, USA.
Aizenman E
No affiliation info available

MeSH

AnimalsCHO CellsCalciumCell SurvivalCricetinaeDizocilpine MaleateKynurenic AcidL-Lactate DehydrogenaseLuciferasesPipecolic AcidsPiperidinesReceptors, N-Methyl-D-AspartateTransfection

Pub Type(s)

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

Language

eng

PubMed ID

8930153

Citation

Boeckman, F A., and E Aizenman. "Pharmacological Properties of Acquired Excitotoxicity in Chinese Hamster Ovary Cells Transfected With N-methyl-D-aspartate Receptor Subunits." The Journal of Pharmacology and Experimental Therapeutics, vol. 279, no. 2, 1996, pp. 515-23.
Boeckman FA, Aizenman E. Pharmacological properties of acquired excitotoxicity in Chinese hamster ovary cells transfected with N-methyl-D-aspartate receptor subunits. J Pharmacol Exp Ther. 1996;279(2):515-23.
Boeckman, F. A., & Aizenman, E. (1996). Pharmacological properties of acquired excitotoxicity in Chinese hamster ovary cells transfected with N-methyl-D-aspartate receptor subunits. The Journal of Pharmacology and Experimental Therapeutics, 279(2), 515-23.
Boeckman FA, Aizenman E. Pharmacological Properties of Acquired Excitotoxicity in Chinese Hamster Ovary Cells Transfected With N-methyl-D-aspartate Receptor Subunits. J Pharmacol Exp Ther. 1996;279(2):515-23. PubMed PMID: 8930153.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacological properties of acquired excitotoxicity in Chinese hamster ovary cells transfected with N-methyl-D-aspartate receptor subunits. AU - Boeckman,F A, AU - Aizenman,E, PY - 1996/11/1/pubmed PY - 1996/11/1/medline PY - 1996/11/1/entrez SP - 515 EP - 23 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 279 IS - 2 N2 - The cytotoxicity induced by the transient expression of functional N-methyl-D-aspartate (NMDA) receptors has been examined with the use of a luciferase reporter assay in Chinese hamster ovary cells. Various NMDA receptor antagonists, in a dose-dependent manner, prevented a loss of luciferase activity 24 to 48 hr post-transfection of either the NR1/NR2A or NR1/ NR2B subunit receptor configurations, likely correlating to the time required to express functionally these receptors. Both glutamate and NMDA were potently cytotoxic to transfected cells previously protected by antagonists. The novel ifenprodil analog (1S,2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol (CP101,606-27) protected cells expressing NR1/NR2B, but not those cells expressing either NR1/NR2A or, putatively, NR1/NR2A/NR2B. Decreased cytotoxicity was observed when a mutated NR1 subunit (N616R) with reduced Ca++ permeability was used in coexpression studies with NR2A or NR2B. In contrast to our results with NR1/NR2A or NR1/NR2B, cells expressing NR1/NR2C did not perish. Our studies suggest that expression of functional NMDA receptors in non-neuronal cells leads to a form of excitotoxicity similar to that observed in mammalian neurons in vitro. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/8930153/Pharmacological_properties_of_acquired_excitotoxicity_in_Chinese_hamster_ovary_cells_transfected_with_N_methyl_D_aspartate_receptor_subunits_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8930153 DB - PRIME DP - Unbound Medicine ER -