AGONISTS OF CYCLIC AMP-COUPLED METABOTROPIC GLUTAMATE RECEPTORS IN ADULT-RAT CORTICAL SLICES

A number of potential Group 2 and Group 3 metabotropic glutamate recep tor (rr,Glu receptor) agonists were investigated in adult rat brain ce rebrocortical slices. The rank order of their potency in inhibiting fo rskolin-stimulated adenylyl cyclase was found to be: (S)-2-amino-2-met hyl-4-phosphonobutyric acid (MAP4) > (2S,1'S,2'S)-2-(2-carboxycyclopro pyl)glycine (L-CCG-I) > (1S,3S)-1-aminocyclopentane-1,3-dicarboxylic a cid (1S,3S-ACPD) > (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid ( 1S,3R)-ACPD) > S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG -IV)> (S)-2-methylglutamate ((S)-MG) > L-glutamate > (2S,1'S,2'S)-2-(2 - carboxycyclopropyl)alanine (MCCG)> L-2-amino-4-phosphonobutyric acid (L-AP4) > L-serine-O-phosphate (SOP). The finding that (S)-2-amino-2- methyl-4-phosphonobutyric acid was the most potent agonist at these me tabotropic glutamate receptors is in contrast to its observed potent m Glu receptor antagonist action in the neonatal rat spinal cord.