Experiments with Kainate and Quisqualate Agonists and Antagonists in Relation to the Sub-Classification of ‘Non-NMDA’ Receptors

The differentiation of “kainate” (K) and “quisqualate” (Q) sub-classes of non-NMDA excitatory amino acid (EAA) (Davies et al., 1979; Watkins, 1978) receptors was originally based on the selective depressant action of L-glutamic acid diethyl ester (GDEE) on quisqualate induced responses in ionophoretic experiments in vivo (McLennan and Lodge, 1979; Watkins and Evans, 1981). This concept was supported by the opposite selectivity shown by other antagonists subsequently developed, e.g., γ -D-glutamylglycine (DGG) (Davies and Watkins, 1985) and γ -D-glutamylaminomethyl sulphonate (GAMS)7, and by the marked differences observed in the relative potencies of kainate and quisqualate in different tissues (Shinozaki, 1978; Agrawal and Evans, 1986). The results of binding studies with 3H-kainate and 3H-L-glutamate under various conditions also generally supported the notion of separate kainate and quisqualate receptors, as did those of later experiments with the quisqualate analogue, 3H-AMPA (Foster and Fagg, 1984; Monaghan et al., 1989). In conformity with this concept, autoradiographic patterns obtained in brain sections with 3H-kainate and 3H-AMPA are quite distinct (Cotman et al., 1987).