NDLI: Lack of interaction between nitric oxide and the redox modulatory site of the NMDA receptor

Content Provider	PubMed Central
Author	Aizenman, Elias Potthoff, William K.
Copyright Year	1999
Abstract	The inhibitory effects of nitric oxide (NO) on N-methyl-D-aspartate (NMDA) receptor function have been proposed to be mediated via the interaction of this gas with a redox-sensitive thiol moiety on the receptor. Here, we evaluated this suggested mechanism by examining the actions of various NO donors on native neuronal receptors as well as in wild-type and cysteine-mutated recombinant NMDA receptors expressed in Chinese hamster ovary (CHO) cells. The NO donor N-ethyl-2-(1-ethyl-2-hydroxy-2-nitrosohydraxino)ethanamine (NOC-12; 100 μM) produced a rapid and readily reversible inhibition of whole-cell currents induced by NMDA (30 μM) in cultured cortical neurons. The inhibition was apparent at all holding potentials, though a more pronounced block was observed at negative voltages. The effects of NOC-12 disappeared when the donor was allowed to expire. A similar receptor block was observed with another NO-releasing agent, S-nitroso-N-acetylpenicillamine (SNAP; 1 mM). The blocking effects of NO released by SNAP, 3-morpholinosydnonimine (SIN-1; 1 mM), and 3-[2-hydroxy-1-(1-methylethyl)-2-nitrosohydrazino]-1-propanamine (NOC-5; 100 μM) on currents mediated by recombinant NR1/NR2B receptors were virtually indistinguishable from those observed on native receptors. Furthermore, mutating cysteines 744 and 798 of NR1, which constitute the principal redox modulatory site of the NR1/NR2B receptor configuration, did not affect the inhibition produced by NO. The NR2A subunit may contribute its own redox-sensitive site. However, the effects of NO on NR1/NR2A receptors were very similar to those seen for all other receptor configurations evaluated. Hence, we conclude that NO does not exert its inhibition of NMDA-induced responses via a modification of any of the previously described redox-sensitive sites on the receptor.
Related Links	http://dx.doi.org/10.1038/sj.bjp.0702295
Ending Page	300
Page Count	5
Starting Page	296
File Format	PDF
ISSN	00071188
Journal	British Journal of Pharmacology
Issue Number	1
Volume Number	126
Language	English
Publisher Date	1999-01-01
Access Restriction	Open
Subject Keyword	Pharmacology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Pharmacology

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