Trans-ACPD, a selective agonist of the phosphoinositide-coupled excitatory amino acid receptor.

Excitatory amino acids (EAA) are thought to mediate their actions through at least five receptor subtypes. Four of these types appear to gate ion channels and have been named for agonists by which they are selectively activated: N-methyl-Daspartate (NMDA), kainate, a-amino-3-hydroxy5-methyl isoxazole-4-propionlc acid (AMPA), quisqualate and 2-amino-4-phosphonobutyrate (AP4). There is now compelling evidence from studies of phospholnositlde (PI) metabolism indicating that there is a fifth distinct EAA receptor class (for references see Monaghan et al., 1989). In both mRNA-injected oocytes and rat Inppocampal slices PI metabolism is activated by Lglutamate, ibotenate and quisqualate. This appears to represent a distinct receptor class because tins site is not activated by NMDA, kainate, AMPA or L-AP4, nor is it blocked by their antagonists. To date, pharmacological analysis of the PIcoupled EAA receptor has been hampered by the absence of a selective agonist. This presents a particular problem for the characterization of this receptor because simultaneous activation of the other EAA receptors (NMDA, kainate or AMPA) along with the PI-coupled receptor can inhibit subsequent PI metabohsm (Palmer et al., 1988). In this study, we report that the glutamate analogue