[3H]Homoquinolinate binds to a subpopulation of NMDA receptors and to a novel binding site

J. C. Brown, H. W. Tse, D. A. Skifter, J. M. Christie, V. J. Andaloro, M. C. Kemp, J. C. Watkins, D. E. Jane, D. T. Monaghan

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

NMDA receptors mediate several important functions in the CNS; however, little is known about the pharmacology, biochemistry, and function of distinct NMDA receptor subtypes in brain tissue. To facilitate the study of native NMDA receptor subpopulations, we have determined the radioligand binding properties of [3H]homoquinolinate, a potential subtype-selective ligand. Using quantitative receptor autoradiography, NMDA-specific [3H]homoquinolinate binding selectively labeled brain regions expressing NR2B mRNA (layers I-III of cerebral cortex, striatum, hippocampus, and septum). NMDA-specific [3H]homoquinolinate binding was low in brain regions that express NR2C and NR2D mRNA (cerebellar granular cell layer, NR2C; glomerular layer of olfactory bulb, NR2C/NR2D; and midline thalamic nuclei, NR2D). In forebrain, the pattern of NMDA-specific [3H]homoquinolinate binding paralleled NR2B and not NR2A distribution. In addition to NMDA- displaceable binding, there was a subpopulation of [3H] homoquinolinate binding sites in the forebrain, cerebellum, and choroid plexus that was not displaced by NMDA or L-glutamate. In contrast, we found that the derivative of homoquinolinate, 2-carboxy-3-carboxymethylquinoline, markedly inhibited the NMDA-insensitive binding of [3H]homoquinolinate without inhibiting the NMDA-sensitive population. [3H]Homoquinolinate may be useful for selectively characterizing NR2B-containing NMDA receptors in a preparation containing multiple receptor subtypes and for characterizing a novel binding site of unknown function.

Original languageEnglish (US)
Pages (from-to)1464-1470
Number of pages7
JournalJournal of Neurochemistry
Volume71
Issue number4
StatePublished - Oct 1 1998

Fingerprint

N-Methyl-D-Aspartate Receptors
N-Methylaspartate
Binding Sites
Brain
Prosencephalon
Midline Thalamic Nuclei
Messenger RNA
Biochemistry
Choroid Plexus
homoquinolinic acid
Olfactory Bulb
Vulnerable Populations
Autoradiography
Cerebral Cortex
Cerebellum
Glutamic Acid
Hippocampus
Cells
Pharmacology
Tissue

Keywords

  • 2-Carboxy-3-carboxymethylquinoline
  • NMDA receptors Brain
  • [H]Homoquinolinate

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Brown, J. C., Tse, H. W., Skifter, D. A., Christie, J. M., Andaloro, V. J., Kemp, M. C., ... Monaghan, D. T. (1998). [3H]Homoquinolinate binds to a subpopulation of NMDA receptors and to a novel binding site. Journal of Neurochemistry, 71(4), 1464-1470.

[3H]Homoquinolinate binds to a subpopulation of NMDA receptors and to a novel binding site. / Brown, J. C.; Tse, H. W.; Skifter, D. A.; Christie, J. M.; Andaloro, V. J.; Kemp, M. C.; Watkins, J. C.; Jane, D. E.; Monaghan, D. T.

In: Journal of Neurochemistry, Vol. 71, No. 4, 01.10.1998, p. 1464-1470.

Research output: Contribution to journalArticle

Brown, JC, Tse, HW, Skifter, DA, Christie, JM, Andaloro, VJ, Kemp, MC, Watkins, JC, Jane, DE & Monaghan, DT 1998, '[3H]Homoquinolinate binds to a subpopulation of NMDA receptors and to a novel binding site', Journal of Neurochemistry, vol. 71, no. 4, pp. 1464-1470.
Brown JC, Tse HW, Skifter DA, Christie JM, Andaloro VJ, Kemp MC et al. [3H]Homoquinolinate binds to a subpopulation of NMDA receptors and to a novel binding site. Journal of Neurochemistry. 1998 Oct 1;71(4):1464-1470.
Brown, J. C. ; Tse, H. W. ; Skifter, D. A. ; Christie, J. M. ; Andaloro, V. J. ; Kemp, M. C. ; Watkins, J. C. ; Jane, D. E. ; Monaghan, D. T. / [3H]Homoquinolinate binds to a subpopulation of NMDA receptors and to a novel binding site. In: Journal of Neurochemistry. 1998 ; Vol. 71, No. 4. pp. 1464-1470.
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abstract = "NMDA receptors mediate several important functions in the CNS; however, little is known about the pharmacology, biochemistry, and function of distinct NMDA receptor subtypes in brain tissue. To facilitate the study of native NMDA receptor subpopulations, we have determined the radioligand binding properties of [3H]homoquinolinate, a potential subtype-selective ligand. Using quantitative receptor autoradiography, NMDA-specific [3H]homoquinolinate binding selectively labeled brain regions expressing NR2B mRNA (layers I-III of cerebral cortex, striatum, hippocampus, and septum). NMDA-specific [3H]homoquinolinate binding was low in brain regions that express NR2C and NR2D mRNA (cerebellar granular cell layer, NR2C; glomerular layer of olfactory bulb, NR2C/NR2D; and midline thalamic nuclei, NR2D). In forebrain, the pattern of NMDA-specific [3H]homoquinolinate binding paralleled NR2B and not NR2A distribution. In addition to NMDA- displaceable binding, there was a subpopulation of [3H] homoquinolinate binding sites in the forebrain, cerebellum, and choroid plexus that was not displaced by NMDA or L-glutamate. In contrast, we found that the derivative of homoquinolinate, 2-carboxy-3-carboxymethylquinoline, markedly inhibited the NMDA-insensitive binding of [3H]homoquinolinate without inhibiting the NMDA-sensitive population. [3H]Homoquinolinate may be useful for selectively characterizing NR2B-containing NMDA receptors in a preparation containing multiple receptor subtypes and for characterizing a novel binding site of unknown function.",
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AU - Andaloro, V. J.

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N2 - NMDA receptors mediate several important functions in the CNS; however, little is known about the pharmacology, biochemistry, and function of distinct NMDA receptor subtypes in brain tissue. To facilitate the study of native NMDA receptor subpopulations, we have determined the radioligand binding properties of [3H]homoquinolinate, a potential subtype-selective ligand. Using quantitative receptor autoradiography, NMDA-specific [3H]homoquinolinate binding selectively labeled brain regions expressing NR2B mRNA (layers I-III of cerebral cortex, striatum, hippocampus, and septum). NMDA-specific [3H]homoquinolinate binding was low in brain regions that express NR2C and NR2D mRNA (cerebellar granular cell layer, NR2C; glomerular layer of olfactory bulb, NR2C/NR2D; and midline thalamic nuclei, NR2D). In forebrain, the pattern of NMDA-specific [3H]homoquinolinate binding paralleled NR2B and not NR2A distribution. In addition to NMDA- displaceable binding, there was a subpopulation of [3H] homoquinolinate binding sites in the forebrain, cerebellum, and choroid plexus that was not displaced by NMDA or L-glutamate. In contrast, we found that the derivative of homoquinolinate, 2-carboxy-3-carboxymethylquinoline, markedly inhibited the NMDA-insensitive binding of [3H]homoquinolinate without inhibiting the NMDA-sensitive population. [3H]Homoquinolinate may be useful for selectively characterizing NR2B-containing NMDA receptors in a preparation containing multiple receptor subtypes and for characterizing a novel binding site of unknown function.

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