CHARACTERIZATION OF 2 CENTRAL AMPA-PREFERRING RECEPTORS HAVING DISTINCT LOCATION, FUNCTION AND PHARMACOLOGY

The existence of a pharmacological heterogeneity among the glutamate r eceptors sensitive to (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) has been investigated in the adult rat central nervo us system (CNS). AMPA stimulated [H-3]noradrenaline ([H-3]NA) release from hippocampal synaptosomes (pD(2) = 4.58) and the production of cGM P in cerebellar slices (pD(2) = 7.75). The AMPA effects in the two sys tems were tested against several glutamate receptor antagonists includ ing 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), 6,7-dinitro-quinoxali ne-2,3-dione (DNQX), L-glutamate diethylester (GDEE), gamma-D-glutamyl -glycine (GDGG) and gamma-D-glutamyl-aminomethylsulphonate (GAMS). In both systems the AMPA effect was equally sensitive to CNQX or DNQX. Ho wever, while the AMPA-evoked increase of [H-3]NA release from presynap tic terminals was not affected by GAMS, GDGG or GDEE, the postsynaptic cGMP response was prevented by GDGG and GDEE. It is concluded that ra t hippocampus and cerebellum possess, respectively, presynaptic and po stsynaptic AMPA-sensitive receptors involved in different functions an d endowed with diverse pharmacological properties.