Effect of magnesium sulfate on excitatory amino acid receptors in the rat brain. II. Kainate and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors.
OBJECTIVE
Our purpose was to determine the effect of peripherally administered magnesium sulfate on kainate and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors in the rat brain.


METHODS
Six rats were injected intraperitoneally with 270 mg/kg magnesium sulfate, followed by 27 mg/kg every 20 minutes for 4 hours. Controls (n = 6) received saline solution. Six rats received intraperitoneal injections of magnesium sulfate (270 mg/kg) every 4 hours for 24 hours and six received saline solution. Then 6 rats received intraperitoneal magnesium sulfate (270 mg/kg) every 12 hours for 2 weeks and six received saline solution. Rats were subsequently perfused and killed; their brains were dissected and frozen. Cryostat sections were labeled in vitro for autoradiography assay. The ligands used were tritiated kainate agonist, kainate binding site; tritiated alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid agonist, and tritiated 6-cyano-7-nitroquinoxaline-2,3-dione antagonist, both at the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid binding site.


RESULTS
Magnesium sulfate caused decreased binding of the agonist to the kainate receptor recognition site after both short-term and intermediate-term systemic administration, whereas long-term treatment resulted in increased binding. No significant consistent effect on the binding to the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor agonist site was recorded after magnesium administration. The receptor antagonist showed an increased binding after short-term treatment. Long-term administration also resulted in increased binding of the antagonist, an effect that was limited to the hippocampus.


CONCLUSIONS
These data suggest down-regulation of the kainate receptor population during short- and intermediate-term magnesium sulfate treatment. However, long-term inhibition by magnesium resulted in up-regulation of the receptor population. The results may also reflect an increased inhibitory effect of magnesium sulfate on the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor.
Hallak
M
M
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48235, USA.
Irtenkauf
S M
SM
Cotton
D B
DB
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008274:Magnesium / Q000097:blood; D008278:Magnesium Sulfate / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000187:drug effects / Q000378:metabolism; D014316:Tritium; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D008274:Magnesium; D008278:Magnesium Sulfate; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D014316:Tritium; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid