Characterization of the metabotropic glutamate receptor in mouse cerebellar granule cells: lack of effect of 2,3-dihydroxy-6-nitro-7-sulphamoylbenzo(F)-quinoxaline (NBQX).
The ability of excitatory amino acids to stimulate phosphoinositide hydrolysis in mouse cerebellar granule cells was characterized. Quisqualic acid (EC50 = 2 microM), ibotenic acid (EC50 = 15 microM), kainic acid (EC50 = 30 microM), glutamate (EC50 = 51 microM) and (1S,3R)-1-amino-cyclo-pentane-1,3-dicarboxylic acid (t-ACPD) (EC50 = 175 microM) dose-dependently stimulated phosphoinositide hydrolysis. The stimulation of phosphoinositide hydrolysis was dose-dependently blocked by 2-amino-3-phosphonopropionic acid (L-AP3) and pertussis toxin, but was unaffected by other excitatory amino acid agonists or antagonists. These data suggest that the pharmacology of excitatory amino acid-stimulated phosphoinositide hydrolysis in the mouse cerebellar granule cells is mediated through the G protein coupled metabotropic glutamate receptor. The overall pharmacology of the metabotropic receptor present in mouse cerebellar granule cells differs from that of previously reported tissue preparations such as rat cerebellar granule cells. In addition, the effect of the alpha-amino-3-hydroxyl-5-methyl-1-isoxazole-4-propionic acid (AMPA) receptor antagonist, 2,3-dihydroxy-6-nitro-7-sulphamoylbenzo(F)quinoxaline (NBQX), on excitatory amino acid-stimulated phosphoinositide hydrolysis was also examined. NBQX was without effect on either basal phosphoinositide hydrolysis or excitatory amino acid-stimulated phosphoinositide hydrolysis, suggesting that the neuroprotective effect of NBQX is not mediated through the metabotropic glutamate receptor.
Suzdak
P D
PD
Department of Receptor Neurochemistry, Novo Nordisk A/S, CNS Division, Maaloev, Denmark.
Sheardown
M J
MJ
Honoré
T
T
D000409:Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000378:metabolism; D006868:Hydrolysis; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism; D007608:Kainic Acid / Q000494:pharmacology; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D037342:Pertussis Toxin; D010716:Phosphatidylinositols / Q000378:metabolism*; D011810:Quinoxalines / Q000494:pharmacology*; D016318:Quisqualic Acid / Q000494:pharmacology; D017470:Receptors, Glutamate / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D011810:Quinoxalines; D017470:Receptors, Glutamate; D010566:Virulence Factors, Bordetella; C000211:2-amino-3-phosphonopropionic acid; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C002647:inositol 1-phosphate; D007051:Ibotenic Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D016318:Quisqualic Acid; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000409:Alanine; D007608:Kainic Acid