Nitric oxide does not modulate kainate receptor binding in human brain.
The ability of three nitric oxide (NO) donor compounds to modify ligand binding to kainate receptors was studied in tissue from human adult autopsy brains. Binding of [3H]kainic acid (5 nM) was measured in frontal cortex membranes made from Brodmann area 8 (BA 8) and autoradiographically using sections of frontal cortex (BA 8 and 9). None of the three donors, S-nitroso-N-acetyl-D,L-penicillamine (SNAP), S-nitrosocysteine (Cys-NO) and 3-morpholinosydnonimine chloride (SIN-1) altered the specific binding of [3H]kainic acid. Nitrite accumulation assays confirmed that adequate amounts of NO were released by the donors under the ligand binding conditions used. The findings show that binding to the kainate receptor, in contrast to the other ionotropic glutamate receptors, is not affected by NO and strongly suggest that endogenous NO produced by NO synthase (NOS) does not modulate kainate receptors in vivo. Mechanisms whereby NOS inhibitors potentiate kainic acid-induced seizures in animal models may include altered modulation of glutamate N-methyl-D-aspartate (NMDA) receptors.
Lees
R D
RD
School of Biological Sciences, University of Manchester, UK. rlees@man.ac.uk
Slater
P
P
D'Souza
S W
SW
D001921:Brain / Q000378:metabolism*; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D018092:Kainic Acid Receptors / Q000378:metabolism*; D026423:S-Nitroso-N-Acetylpenicillamine; D026403:S-Nitrosothiols
D003545:Cysteine; D008981:Molsidomine; D009569:Nitric Oxide; D010396:Penicillamine; D018092:Kainic Acid Receptors; D026423:S-Nitroso-N-Acetylpenicillamine; D026403:S-Nitrosothiols; C002385:linsidomine; C021315:S-nitrosocysteine