Characterization of the Quisqualate Receptor Linked to Phosphoinositide Hydrolysis in Neurocortical Cultures

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Abstract
Activation of phosphoinositide metabolism is an early event in signal transduction for a number of neurotransmitters and hormones. In primary cultures of rat neurocortical cells, various excitatory amino acids stimulate inositol phosphate production with a rank order of potency of quisqualate > ibotenate > glutamate > kainate, N-methyl-D-aspartate > .alpha.-amono-3-hydroxyl-5-methyl-4-isoxazole propionate. This response to excitatory amino acids was insensitive to a variety of excitatory amino acid antagonists including 6-cyano-7-nitroquinoxaline-2,3-dione, 3-3(2-carboxypiperazine-4-yl)propyl-1-phosphonate, and 2-amino-4-phosphonobutyrate. The individual responses of quisqualate-, ibotenate-, and kainate-stimulated inositil phosphate production were not additive. These results suggest that phosphoinositide metabolism activated by excitatory amino acids is mediated by a unique quesiqualate-preferring receptor that is not antagonized by known N-methyl-D-aspartate and non-N-methyl-D-aspartate antagnonist, and is relatively insensitive to .alpha.-amino-3-hydroxyl-5-methyl-4-isoxazole propionate.