Two classes of N-methyl-D-aspartate recognition sites: differential distribution and differential regulation by glycine.

Monaghan, Daniel T.; Olverman, Henry J.; Nguyen, Long V.; Watkins, Johnathan; Cotman, Carl W.

doi:10.1073/pnas.85.24.9836

Cited by 398 publications

(123 citation statements)

References 30 publications

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“…1B). Agonistpreferring NMDA receptors defined as NMDA-specific L-~H-glutamate binding in the presence of 6 MM D-AP5 displayed lower relative density levels in lateral thalamic nuclei than NMDAspecific L-'H-glutamate binding, consistent with our previous findings (Monaghan et al, 1988).…”

Section: Resultssupporting

confidence: 82%

“…(1) agonist-preferring and (2) antagonist-preferring NMDA receptors (Monaghan et al, 1988;Honor& et al, 1989;Monaghan, 199 1;Sakurai et al, 1993) (3) cerebellar NMDA receptors with distinctive pharmacological properties (Perkins and Stone, 1983;Sekiguchi et al, 1990;Ebert et al, 199 1;Monaghan and Beaton, 1991;O'Shea et al, 1991;Yoneda and Ogita, 1991;Beaton et al, 1992) and (4) with other, unique pharmacological properties (Beaton et al, 1992). The results ofthis report demonstrate that the anatomical distributions of each of the four subtypes show striking parallels to the distributions of individual NR2 subunit mRNAs and that the NR2 subunit is of critical importance in determining receptor subtype pharmacology.…”

Section: Discussionmentioning

confidence: 99%

“…'H-(*)-2-carboxypiperazine-4-yl-propyl-1 -phosphonic acid ('H-CPP, 25 Ci/mmol; New England Nuclear, Boston, MA) autoradiography was performed as described (Monaghan et al, 1988). Following two 10 min preincubations at 3O"C, slide-mounted sections were incubated in 50 mM Tris-Cl, containing 100 nM 3H-CPP for 20 min at 0°C.…”

Section: Methodsmentioning

confidence: 99%

“…Two of these populations are typified by NMDA receptors found in the cerebellum (Perkins and Stone, 1983;Sekiguchi et al, 1990;Ebert et al, 199 I;Monaghan and Beaton, 199 1;O'Shea et al, 1991;Beaton et al, 1992) and the medial thalamic nuclei (Beaton et al, 1992) which display distinct pharmacological profiles at both the glutamate and channel blocker binding sites. The two remaining groups of NMDA receptors differ in their relative affinities for agonists and antagonists (Monaghan et al, 1988;Monaghan, 1991;Sakurai et al, 1993) as well as in specific biochemical properties Cunningham and Michaelis, 1990;Ogita et al, 199 1). Examples of these NMDA receptor subtypes are the NMDA receptors in the ventral posterior nucleus of the lateral thalamus that display a relatively high affinity for antagonists (antagonist-preferring receptor) and those of the medial striatum that display a higher affinity for agonists (agonist-preferring receptor).…”

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confidence: 99%

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The molecular basis of NMDA receptor subtypes: native receptor diversity is predicted by subunit composition

et al. 1994

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The relationship between four pharmacologically distinct NMDA receptor subtypes, identified in radioligand binding studies, and the recently identified NMDA receptor subunits (NR1a-g, NR2A-D) has not been determined. In this report, we demonstrate that the anatomical distribution of the four NMDA receptor subtypes strikingly parallels the distribution of mRNA encoding NR2A-D subunits. The distribution of NR2A mRNA was very similar to that of “antagonist-preferring” NMDA receptors [defined by high-affinity 3H-2-carboxypiperazine-4-yl-propyl- 1-phosphonic (3H-CPP) binding sites; correlation coefficient = 0.88]. Agonist-preferring NMDA receptors localized to brain regions expressing both NR2B mRNA and NR1- mRNA (NR1 splice variant lacking insert 1). NR2C mRNA was largely restricted to the cerebellar granule cell layer, a region that displays a unique pharmacological profile. NR2D mRNA localized exclusively to those diencephalic nuclei that have a fourth, distinct pharmacological profile (typified by the midline thalamic nuclei). The pharmacology of native NMDA receptors was compared to that of heteromeric NMDA receptors expressed in Xenopus oocytes (NR1/NR2A, NR1/NR2B, NR1/NR2C). The oocyte-expressed NR1/NR2A receptor displayed a higher affinity for antagonists and a slightly lower affinity for agonists than the NR1/NR2B receptor. These patterns are analogous to those found for radioligand binding to native receptors in the lateral thalamus and medial striatum, respectively. NMDA receptors in the lateral thalamus (with a high density of NR2A subunit mRNA) displayed higher affinity for antagonists and a lower affinity for agonists than did NMDA receptors of the medial striatum (a region rich in NR2B mRNA). Relative to the NR1/NR2A and NR1/NR2B receptors, oocyte-expressed NR1/NR2C receptors had a lower affinity specifically for both D-3-(2- carboxypiperazin-4-yl)-1-propenyl-1-phosphonic acid (D-CPPene) and homoquinolinate (HQ). This pattern was identical to that observed for cerebellar (NR2C-containing) versus forebrain (NR2A- and NR2B- containing) NMDA receptors. Taken together, the data in this report suggest that the four previously identified native NMDA receptor subtypes differ in their NR2 composition. Furthermore, the NR2 subunits significantly contribute to the anatomical and pharmacological diversity of NMDA receptor subtypes.

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Section: Resultssupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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The molecular basis of NMDA receptor subtypes: native receptor diversity is predicted by subunit composition

et al. 1994

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“…Thus the participation of both S1 and S2 regions possibly provided by a closed form seems to be predictable for agonist binding. Because our NR1 subunits show a decreased affinity for agonists, the homomeric NR1 proteins might exist in an open form, namely an antagonistpreferring form as postulated [25,26]. Co-expression with NR2 subunits is expected to improve the affinity for agonist.…”

Section: Discussionmentioning

confidence: 99%

Expression and characterization of a glycine-binding fragment of the N-methyl-D-aspartate receptor subunit NR1

Miyazaki¹,

Nakanishi

Jingami³

1999

Biochemical Journal

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N-Methyl--aspartate receptor channels are composed of an NR1 subunit and at least one of the NR2 subunits (NR2A-D). Activation of the N-methyl--aspartate receptor requires the coagonists glycine and glutamate. It has been proposed that the NR1 subunit possesses a glycine-binding site. We have expressed a soluble form of the NR1 subunit, which was produced by connecting the N-terminal extracellular region with the extracellular loop between the third and fourth membrane segments, by a baculovirus system along with full-length and truncated membrane-bound forms. The soluble NR1 receptor was efficiently secreted into the culture medium and showed a high affinity for ligands. The K d of a glycine-site antagonist, [$H]MDL 105,519[(E)-3-(2-phenyl-2-carboxyethenyl)-4,6-dichloro-1H-indole-2-carboxylic acid], for the soluble receptor was 3.89p0.97 nM, which was comparable to the K d of 4.47p1.39 nM for the membrane-bound full-length form. These values were close to the values reported previously with the use

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Synchronized overproduction of AMPA, kainate, and NMDA glutamate receptors during human spinal cord development

Kalb

Fox

1997

J. Comp. Neurol.

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Quantitative receptor autoradiography was used to map the distribution in the developing human spinal cord of the three types of ionotropic glutamate receptors. N-methyl-D-Aspartate (NMDA) receptors were labeled with [3H]glutamate, kainic acid (KA) receptors were labeled with [3H]KA, and alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionate (AMPA) receptors were labeled with [3H]AMPA. In the adult, labeling of all three receptor subtypes is largely restricted to the substantia gelatinosa (SG) in the dorsal horn, with very low level labeling elsewhere in the spinal gray matter. In marked distinction, in late fetal life, high level ligand binding is seen throughout the spinal gray matter. In early postnatal life, binding sites diminish in all regions, but least so in the SG, until the adult pattern emerges. Thus a coordinated transient high level of ionotropic glutamate receptor expression occurs within the developing spinal cord. Saturation analysis of ligand binding shows that the affinity of [3H]KA and [3H]AMPA binding is not developmentally regulated. In contrast, the affinity of [3H]glutamate binding to the NMDA receptor in the fetal ventral horn is three-fold greater than in the adult ventral horn. Thus, in addition to quantitative changes in glutamate receptor expression, qualitative changes occur in the expression of NMDA receptors during development. The distinct glutamate receptor phenotype of fetal and early postnatal spinal cord cells suggests that alterations in the excitable properties of these cells plays an important role in activity-dependent development and in susceptibility to excitotoxic injury.

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Two classes of N-methyl-D-aspartate recognition sites: differential distribution and differential regulation by glycine.

Cited by 398 publications

References 30 publications

The molecular basis of NMDA receptor subtypes: native receptor diversity is predicted by subunit composition

The molecular basis of NMDA receptor subtypes: native receptor diversity is predicted by subunit composition

Expression and characterization of a glycine-binding fragment of the N-methyl-D-aspartate receptor subunit NR1

Synchronized overproduction of AMPA, kainate, and NMDA glutamate receptors during human spinal cord development

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