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Down-Regulation of AMPA Glutamate Receptors Reduces Cerebrocortical Metabolic Response to Stimulation

Neurochemical Research volume 29, pages 1425–1430 (2004)Cite this article

Abstract

We tested the hypothesis that chronic stimulation of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate) glutamate receptors with an agonist causes down-regulation of the receptor protein and a decrement in basal and/or stimulated cerebral O2 consumption. Male Wistar rats were intradurally infused with 10 μm AMPA by an osmotic pump at a rate of 1 μl/h for 6 days. As a result, the specific binding of (S)-[3H]-5-fluorowillardiine to AMPA receptors in the cerebral cortex decreased 46% from 2.7 ± 0.3 to 1.5 ± 0.6 (density units). Under isoflurane anesthesia and after topical stimulation to the right cerebral cortex with 10−3 M AMPA, cerebral blood flow (14C-iodoantipyrine method) and O2 consumption (cryomicrospectrophotometrically determined) were determined in control and down-regulated rats. Down-regulation of AMPA receptors did not alter basal O2 consumption. In control, after agonist stimulation, the O2 consumption in the ipsilateral cortex increased by 34%, (4.7 ± 0.5 ml O2 · min−1 · 100 g−1 compared to 3.5 ± 0.4 in the contralateral cortex). In the down-regulated rats, the O2 consumption did not significantly increase (4.0 ± 1.5 ml O2 · min−1 · 100 g−1 compared to 3.3 ± 1.7 in the contralateral cortex) after AMPA. In conclusion, following chronic simulation, AMPA receptors underwent down-regulation, but such down-regulation did not alter basal cerebrocortical blood flow or O2 consumption. AMPA down-regulation reduced the agonist stimulated increase in cortical O2 consumption.

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Affiliations

  1. Department of Physiology & Biophysics, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey

    Arabinda K. Sinha, Romeu Azevedo & Harvey R. Weiss

  2. Department of Anesthesiology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey

    Oak Z. Chi

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  1. Arabinda K. Sinha
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  2. Romeu Azevedo
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  3. Oak Z. Chi
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  4. Harvey R. Weiss
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Correspondence to Arabinda K. Sinha.

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Sinha, A.K., Azevedo, R., Chi, O.Z. et al. Down-Regulation of AMPA Glutamate Receptors Reduces Cerebrocortical Metabolic Response to Stimulation. Neurochem Res 29, 1425–1430 (2004). https://doi.org/10.1023/B:NERE.0000026407.36663.e4

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  • DOI: https://doi.org/10.1023/B:NERE.0000026407.36663.e4

  • Cerebral blood flow
  • cerebral O2 consumption
  • excitatory amino acid