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( R,S )‐α‐Amino‐3‐Hydroxy‐5‐Methylisoxazole‐4‐Propionic Acid (AMPA) Receptors Mediate a Calcium‐Dependent Inhibition of the Metabotropic Glutamate Receptor‐Stimulated Formation of Inositol 1,4,5‐Trisphosphate
Author(s) -
Lonart Gyorgy,
Alagarsamy Sudarkodi,
Johnson Kenneth M.
Publication year - 1993
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1993.tb13398.x
Subject(s) - ampa receptor , acpd , metabotropic glutamate receptor , metabotropic receptor , metabotropic glutamate receptor 1 , chemistry , glutamate receptor , calcium , biology , biochemistry , receptor , organic chemistry
l ‐Glutamate (3‐1,000 μ M ) and (1S,3R)‐l‐aminocyclopentane‐1,3‐dicarboxylic acid (1S.3R‐ACPD; 10‐1,000 μ M ), a selective agonist for the metabotropic glutamate receptor, stimulated the formation of inositol 1,4,5‐trisphosphate in a concentration‐dependent manner. l ‐Glutamate was half as efficacious as 1S,3R‐ACPD. N ‐methyl‐ d ‐aspartate (nMDA; 1 n M to 1 m M ) did not significantly influence the response to a maximally effective concentration of 1S,3R‐ACPD (100 μ M ). On the other hand, coapplication of (R,S)‐α‐amino‐3‐hydroxy‐5‐methylisoxa‐zole‐4‐propionic acid (AMPA; 1‐300 n M ) produced a concentration‐ and time‐dependent inhibition of the 1S,3R‐ACPD effect, with a maximal inhibition (97%) at 100 n M . Ten micromolar 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione. an antagonist of the AMPA receptor, blocked the inhibitory effect of AMPA. Reduced extracellular calcium concentration, as well as 10 μ M nimodipine, an l ‐type calcium channel antagonist, inhibited the AMPA influence on the 1S,3R‐ACPD response. W‐7, a calcium/calmodulin antagonist, prevented the inhibition by AMPA. whereas H‐7. an inhibitor of protein kinase C, had no effect. These data suggest that activation of AMPA receptors has an inhibitory influence on inositol 1,4,5‐trisphosphate formation mediated by stimulation of the metabotropic glutamate receptor. The mechanism of action involves calcium influx through l ‐type calcium channels and possible activation of calcium/calmodulin‐dependent enzymes.