Effect of up-regulation of NMDA receptors on cerebral O2 consumption and blood flow in rat.
We tested the hypothesis that cerebrocortical blood flow and O2 consumption would be proportional to an up-regulated number of functional N-methyl-D-aspartate (NMDA) receptors. Previous work had shown a relationship between cerebral metabolism and NMDA receptor activity. We increased the specific binding to NMDA receptors in the cerebral cortex, from 2.2 +/- 0.9 to 4.5 +/- 0.8 (density units) in male Long-Evans rats by daily giving two intraperiotoneal injections (30 mg/kg) of CGS-19755, an NMDA receptor inhibitor, for 7 consecutive days (discontinued for 20 h before experiment). Twelve up-regulated (CGS treated) and 12 control rats were used in this study. Under isoflurane anesthesia and after topical stimulation of the right cerebral cortex with 10(-2) M NMDA, the blood flow (14C-iodoantipyrine method) increased from 98 +/- 11 ml/min/100 g in the unstimulated cortex of the control rats to 161 +/- 37 ml/min/100 g in the stimulated cortex. The unstimulated value for blood flow (95 +/- 7 ml/min/100 g) did not change in the upregulated group but it doubled (194 +/- 69 ml/min/100 g) in the stimulated, upregulated cortex. Similarly, O2 consumption (cryomicrospectrophotometrically determined) in normal rats increased 46%, from 9.3 +/- 1 ml/min/100 g to 13.6 +/- 4 after NMDA stimulation. While in the upregulated animals, O2 consumption increased 103% from 7.9 +/- 0.6 to 16 +/- 6.5 after NMDA stimulation. In conclusion, NMDA receptor upregulation does not alter basal cerebrocortical blood flow or O2 consumption but in the NMDA-stimulated cortex, the blood flow and O2 consumption increase is dependent on the number of NMDA receptors present.
Weiss
H R
HR
Department of Physiology and Biophysics, University of Medicine and Densitry of New Jersey, Robert Wood Johnson Medical School, Piscataway 08854-5635, USA.
Sinha
A K
AK
Lu
X
X
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005740:Gases / Q000097:blood; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D010875:Pipecolic Acids / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015854:Up-Regulation
D018691:Excitatory Amino Acid Antagonists; D005740:Gases; D010875:Pipecolic Acids; D016194:Receptors, N-Methyl-D-Aspartate; C053672:selfotel; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate