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The Journal of Neuroscience, March 1, 1998, 18(5):1725-1734
NMDAR1 Glutamate Receptor Subunit Isoforms in Neostriatal,
Neocortical, and Hippocampal Nitric Oxide Synthase Neurons
Sara W.
Weiss1,
David
S.
Albers1,
Michael J.
Iadarola2,
Ted M.
Dawson3, 4,
Valina L.
Dawson3, 4, 5, and
David G.
Standaert1
1 Neurology Service, Massachusetts General Hospital and
Harvard Medical School, Boston, Massachusetts 02114, 2 Pain
and Neurosensory Mechanisms Branch, National Institute for Dental
Research, Bethesda, Maryland 20892, and Departments of
3 Neurology, 4 Neuroscience, and
5 Physiology, Johns Hopkins University School of Medicine,
Baltimore, Maryland 21287
Nitric oxide (NO), an unconventional and diffusible
neurotransmitter, is synthesized by nitric oxide synthase (NOS). NMDA glutamate receptors are potent regulators of NO synthesis. We have used
dual-label immunofluorescence and confocal microscopy to examine
forebrain neurons in the rat that contain high levels of neuronal NOS
(nNOS) for the presence of the NMDAR1 receptor subunit protein and
regions of this protein encoded by three alternative spliced segments
of the NMDAR1 mRNA: N1, C1, and C2. In the neostriatum, neocortex, and
hippocampus, nNOS-labeled neurons exhibit strong NMDAR1
immunoreactivity (-ir). In all three of these regions, nNOS-positive
neurons are characterized by the absence of immunoreactivity for the C1
segment of NMDAR1, whereas C1-ir is abundant in most nNOS-negative
neurons. In addition, nNOS-ir neurons exhibit selective staining for
the alternative C2' terminus of NMDAR1 that is produced when the C2
segment is absent. These results demonstrate directly that neurons with
abundant nNOS-ir contain NMDAR1 receptor subunit proteins and that the
NMDAR1 isoforms present in these cells differ from those of most other
neurons in these regions. The distinct NMDA receptor phenotype of these
nNOS-positive neurons is likely to contribute to both the physiological
regulation of NO release by glutamate as well as to NO-mediated
excitotoxic injury.
Key words:
NMDAR1; alternative splicing; nitric oxide synthase; striatum; hippocampus; cerebral cortex
Copyright © 1998 Society for Neuroscience 0270-6474/98/1851725-10$05.00/0
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