CGP 39653 binding in the chick CNS after NMDA receptor antagonist treatment

White, Benjamin H.; Vogel, Michael W.

doi:10.1007/bf01271185

Cited by 8 publications

(7 citation statements)

References 12 publications

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“…Thus the rates of association and dissociation of [ 3 H]CGP 39653, as well as the K D value for this ligand, are similar in chick (present study) and rodent (Sills et al 1991;Reynolds 1994) cerebral cortex. The B max values for the binding are consistent with the values of 65 and 131 fmol/mg tissue for cerebellar and forebrain regions of E20 chicks in an autoradiographic study using 90 nM [ 3 H]CGP 39653 (White and Vogel 1996).…”

Section: Discussionsupporting

confidence: 61%

“…Whether these differences are due to tissue or species differences is unclear, since data on chick brain glutamate receptors and their function are limited to autoradiographic data with [ 3 H]CGP 39653 for embryonic chicks (White and Vogel 1996), [ 3 H]glutamate binding data for hyperstriatum ventriale membranes 15-30 h after hatching (McCabe and Horn 1988), and [ 3 H]MK-801 and calcium uptake data for 11-day-old and 8-week-old chicks (Kavanagh et al 1991). In consequence, in the present study, the functional and pharmacological properties of the NMDA receptor expressed on neurons in embryonic chick telencephalon have been investigated.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of the N-methyl-d-aspartate (NMDA) receptor in the embryonic chick brain

Jacobsson

Hedin

Sellström

et al. 1998

Naunyn-Schmiedeberg's Arch Pharmacol

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Relatively little is known about the properties of the NMDA receptor in avian species. In the present study, NMDA receptor pharmacology and function has been studied in the embryonic chick brain. The competitive antagonist ligand [3H]CGP 39653 bound to telencephali membranes from 17-day-old chick embryos with KD and Bmax values of 6.6 nM and 3.3 pmol/mg protein, respectively. The binding was inhibited by CGS 19755, L-glutamate, R-CPP and D-AP5 with pI50 values of 7.57, 7.49, 7.28 and 7.08, respectively. L-glycine, S-AMPA, kainate and MK-801 only weakly affected the binding. The inhibitory potency of NMDA (pI50 value 6.98), however, was greater than seen in other species, suggesting a species difference in receptor structure. Such a possibility was investigated by use of two NMDA-R1 antibodies, AB 1516 and 69921 A, which recognize the C-terminal region and an intracellular domain of the rat receptor, respectively. Immunoreactive signals (approximately 116 kDa) were found for a rat brain homogenate, whereas only 69921A gave an immunoreactive signal in the chick. The functional status of the NMDA receptors was investigated in serum-free cultures of neurons from 8-day-old chick embryos. Glutamate and NMDA were found concentration-dependently, and in a manner that could be antagonized by CGS 19755 and MK-801, to produce cell death. Thus, the present study indicates that chick embryonic brain expresses functional NMDA receptors that are pharmacologically and possibly structurally different from their rodent counterparts.

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Section: Discussionsupporting

confidence: 61%

Section: Introductionmentioning

confidence: 99%

Characterization of the N-methyl-d-aspartate (NMDA) receptor in the embryonic chick brain

Jacobsson

Hedin

Sellström

et al. 1998

Naunyn-Schmiedeberg's Arch Pharmacol

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“…The conditions to determine binding to NMDA, AMPA, and kainate receptors have been previously described in detail (Healy et al, 1998;Healy and Meador-Woodruff, 1999;Ibrahim et al, 2000a, b), and used established receptor autoradiography assays methods (Huettner and Bean, 1988;Ransom and Stec, 1988;Sills et al, 1991;Hashimoto et al, 1994;Baron et al, 1996;Siegel et al, 1996;White and Vogel, 1996). We examined multiple binding sites on the NMDA receptor, including the intrachannel site (visualized with […”

Section: Receptor Autoradiographymentioning

confidence: 99%

Abnormal Glutamate Receptor Expression in the Medial Temporal Lobe in Schizophrenia and Mood Disorders

Beneyto

Kristiansen

Oni-Orisan

et al. 2007

Neuropsychopharmacol

380

216

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Pharmacological and anatomical evidence suggests that abnormal glutamate neurotransmission may be associated with the pathophysiology of schizophrenia and mood disorders. Medial temporal lobe structural alterations have been implicated in schizophrenia and to a lesser extent in mood disorders. To comprehensively examine the ionotropic glutamate receptors in these illnesses, we used in situ hybridization to determine transcript expression of N-methyl-D-aspartate (NMDA), a-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), and kainate receptor subunits in the medial temporal lobe of subjects with schizophrenia, bipolar disorder (BD), or major depression (MDD). We used receptor autoradiography to assess changes in glutamate receptor binding in the same subjects. Our results indicate that there are region-and disorder-specific abnormalities in the expression of ionotropic glutamate receptor subunits in schizophrenia and mood disorders. We did not find any changes in transcript expression in the hippocampus. In the entorhinal cortex, most changes in glutamate receptor expression were associated with BD, with decreased GluR2, GluR3, and GluR6 mRNA expression. In the perirhinal cortex we detected decreased expression of GluR5 in all three diagnoses, of GluR1, GluR3, NR2B in both BD and MDD, and decreased NR1 and NR2A in BD and MDD, respectively. Receptor binding showed NMDA receptor subsites particularly affected in the hippocampus, where MK801 binding was reduced in schizophrenia and BD, and MDL105,519 and CGP39653 binding were increased in BD and MDD, respectively. In the hippocampus AMPA and kainate binding were not changed. We found no changes in the entorhinal and perirhinal cortices. These data suggest that glutamate receptor expression is altered in the medial temporal lobe in schizophrenia and the mood disorders. We propose that disturbances in glutamate-mediated synaptic transmission in the medial temporal lobe are important factors in the pathophysiology of these severe psychiatric illnesses.

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“…Receptor autoradiography was carried out under saturating conditions of ligand using assays that have been previously described in detail (Huettner and Bean, 1988;Ransom and Stec, 1988;Sills et al, 1991;Hashimoto et al, 1994;Baron et al, 1996;Siegel et al, 1996;White and Vogel, 1996;Healy et al, 1998;Healy and Meador-Woodruff, 1999;Ibrahim et al, 2000a, b …”

Section: Receptor Autoradiographymentioning

confidence: 99%

Lamina-Specific Abnormalities of NMDA Receptor-Associated Postsynaptic Protein Transcripts in the Prefrontal Cortex in Schizophrenia and Bipolar Disorder

Beneyto

Meador‐Woodruff

2007

Neuropsychopharmacol

235

141

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The hypothesis of N-methyl-D-aspartate (NMDA) receptor hypofunction in schizophrenia was initially based on observations that blockade of the NMDA subtype of glutamate receptor by noncompetitive antagonists, such as phencyclidine and ketamine, can lead to clinical symptoms similar to those present in schizophrenia. Recently, glutamate has also been implicated in the pathophysiology of the mood disorders. As impaired NMDA receptor activity may be the result of a primary defect in the NMDA receptors themselves, or secondary to dysfunction in the protein complexes that mediate their signaling, we measured expression of both NMDA subunits and associated postsynaptic density (PSD) proteins (PSD95, neurofilament-light (NF-L), and SAP102) transcripts in the dorsolateral prefrontal cortex in subjects with schizophrenia, bipolar disorder, major depression, and a comparison group using tissue from the Stanley Foundation Neuropathology Consortium. We found decreased NR1 expression in all three illnesses, decreased NR2A in schizophrenia and major depression, and decreased NR2C in schizophrenia. We found no changes of NR2B or NR2D. Receptor autoradiography revealed no alterations in receptor binding in any of the illnesses, indicating no change in total receptor number, but taken with the subunit data suggests abnormal receptor stoichiometry. In the same subjects, PSD95 was unchanged in all three illnesses, while reduced NF-L expression was found in schizophrenia, especially in large cells of layer V. SAP102 expression was reduced in bipolar disorder restricted to small cells of layer II and large cells of layer III in bipolar disorder. These alterations likely reflect altered signaling cascades associated with glutamate-mediated neurotransmission within specific cortical circuits in these psychiatric illnesses.

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CGP 39653 binding in the chick CNS after NMDA receptor antagonist treatment

Cited by 8 publications

References 12 publications

Characterization of the N-methyl-d-aspartate (NMDA) receptor in the embryonic chick brain

Characterization of the N-methyl-d-aspartate (NMDA) receptor in the embryonic chick brain

Abnormal Glutamate Receptor Expression in the Medial Temporal Lobe in Schizophrenia and Mood Disorders

Lamina-Specific Abnormalities of NMDA Receptor-Associated Postsynaptic Protein Transcripts in the Prefrontal Cortex in Schizophrenia and Bipolar Disorder

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