ISSN:
1471-4159
Quelle:
Blackwell Publishing Journal Backfiles 1879-2005
Thema:
Medizin
Notizen:
Abstract: The effects of excitatory amino acid agonists and α-amino-ω-phosphonocarboxylic acid antagonists on phosphoinositide hydrolysis in hippocampal slices of the 7-day neonatal rat were examined. Significant stimulation of [3H]inositol monophosphate formation was observed with ibotenate, quisqualate, l-glutamate, l-aspartate, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, l-homocys-teate, and kainate. N-Methyl-D-aspartate had no effect. Of these agonists, ibotenate and quisqualate were the most potent and efficacious. Stimulations by ibotenate and quisqualate were partially inhibited by l-2-amino-4-phosphonobutyrate (10−3M), but this antagonist had no effect on l-glutamate, α-amino-3-hydroxy-5-methyl-4-isoxazoIepropionic acid, or kainate. At 10−3M, D,L-2-amino-3-phosphonopropionate completely inhibited ibotenate and quisqualate stimulations, partially inhibited l-glutamate stimulation, and had no effect on α - amino -3- hydroxy -5- methyl -4- isoxazolepropionic acid-, kainate-, or carbachol-induced [3H]inositol monophosphate formation. Concentration-effect experiments showed D,L-2-amino-3-phosphonopropionate to be five times more potent as an antagonist of ibotenate-stimulated phosphoinositide hydrolysis than L-2-amino-4-phosphonobuty-rate. Thus in the neonatal rat hippocampus, like in the adult rat brain, D,L-2-amino-3-phosphonopropionate is a selective and relatively potent inhibitor of excitatory amino acid-stimulated phosphoinositide hydrolysis. Because this glutamate receptor is uniquely sensitive to D,L-2-amino-3-phosphono-propionate, these studies provide further pharmacological evidence for the existence of a novel excitatory amino acid receptor subtype that is coupled to phosphoinositide hydrolysis in brain.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1111/j.1471-4159.1989.tb09254.x
