PHARMACOLOGICAL PROPERTIES OF ACQUIRED EXCITOTOXICITY IN CHINESE-HAMSTER OVARY CELLS TRANSFECTED WITH N-METHYL-D-ASPARTATE RECEPTOR SUBUNITS

The cytotoxicity induced by the transient expression of functional N-m ethyl-D-aspartate (NMDA) receptors has been examined with the use of a luciferase reporter assay in Chinese hamster ovary cells. Various NMD A receptor antagonists, in a dose-dependent manner, prevented a loss o f 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 glu tamate and NMDA were potently cytotoxic to transfected cells previousl y protected by antagonists. The novel ifenprodil analog henyl)-2-(4-hy droxy-4-phenylpiperidino)-1-propanol (CP101,606-27) protected cells ex pressing 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 wi th NR1/NR2A or NR1/NR2B, cells expressing NR1/NR2C did not perish. Our studies suggest that expression of functional NMDA receptors in non-n euronal cells leads to a form of excitotoxicity similar to that observ ed in mammalian neurons in vitro.