Down-regulation of AMPA glutamate receptors reduces cerebrocortical metabolic response to stimulation.
We tested the hypothesis that chronic stimulation of AMPA (alpha-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 microM AMPA by an osmotic pump at a rate of 1 microl/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 x min(-1) x 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 x min(-1) x 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.
Sinha
Arabinda K
AK
Department of Physiology & Biophysics, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854-5635, USA. sinhaak@umdnj.edu
Azevedo
Romeu
R
Chi
Oak Z
OZ
Weiss
Harvey R
HR
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D007263:Infusions, Parenteral; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000235:genetics*; D012039:Regional Blood Flow / Q000187:drug effects; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000008:administration & dosage / Q000494:pharmacology*
D018091:Receptors, AMPA; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid