Characterization of two central AMPA-preferring receptors having distinct location, function and pharmacology

Abstract

The existence of a pharmacological heterogeneity among the glutamate receptors sensitive to (RS)-α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) has been investigated in the adult rat central nervous system (CNS). AMPA stimulated [³H]noradrenaline ([³H]NA) release from hippocampal synaptosomes (pD₂ = 4.58) and the production of cGMP in cerebellar slices (pD₂ = 7.75). The AMPA effects in the two systems were tested against several glutamate receptor antagonists including 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), 6,7-dinitro-quinoxaline-2,3-dione (DNQX),l-glutamate diethylester (GDEE), γ-d-glutamyl-glycine (GDGG) and γ-d-glutamyl-aminomethylsulphonate (GAMS). In both systems the AMPA effect was equally sensitive to CNQX or DNQX. However, while the AMPA-evoked increase of [³H]NA release from presynaptic terminals was not affected by GAMS, GDGG or GDEE, the postsynaptic cGMP response was prevented by GDGG and GDEE. It is concluded that rat hippocampus and cerebellum possess, respectively, presynaptic and post-synaptic AMPA-sensitive receptors involved in different functions and endowed with diverse pharmacological properties.