Characterization of the quisqualate receptor linked to phosphoinositide hydrolysis in neurocortical cultures.
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 greater than ibotenate greater than glutamate greater than kainate, N-methyl-D-aspartate greater than alpha-amino-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 inositol phosphate production were not additive. These results suggest that phosphoinositide metabolism activated by excitatory amino acids is mediated by a unique quisqualate-preferring receptor that is not antagonized by known N-methyl-D-aspartate and non-N-methyl-D-aspartate antagonists, and is relatively insensitive to alpha-amino-3-hydroxyl-5-methyl-4-isoxazole propionate.
Patel
J
J
Department of Pharmacology, ICI Americas Inc., Wilmington, Delaware 19897.
Moore
W C
WC
Thompson
C
C
Keith
R A
RA
Salama
A I
AI
D000596:Amino Acids / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D006868:Hydrolysis; D007295:Inositol Phosphates / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D018091:Receptors, AMPA; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000187:drug effects; D017981:Receptors, Neurotransmitter / Q000378:metabolism*
D000596:Amino Acids; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D018091:Receptors, AMPA; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; D017981:Receptors, Neurotransmitter