AMPA receptors, function

Antagonists selective for kainate receptors are not available yet. The non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) blocks AMPA as well as kainate receptors. Nevertheless, compounds like GYKI53655, which acts as a noncompetitive antagonist of AMPA receptors and completely blocks AMPA receptor function at certain concentrations at which no antagonistic effect on kainate receptors is discernible, has been used to demonstrate the kainate receptor-mediated currents in neurons. 

Because AMPA receptors function in concert with NMDA receptors, they have been proposed as alternative therapeutic targets in schizophrenia. AMPAkines function as positive allosteric modulators of AMPA receptor-mediated neurotransmission, and facilitate learning and memory in both human (Ingvar et al., 1997) and animal (Hampson et al., 1998) models. Further, these drugs act synergistically with antipsycho-tics to reverse amphetamine-induced hyperactivity (Johnson et al., 1999). 

Schluter OM, Xu W, Malenka RC. 2006. Alternative N-terminal domains of PSD-95 and SAP97 govern activity-dependent regulation of synaptic AMPA receptor function. Neuron 51 99-111. 

Banke TG, Bowie D, Lee H, Huganir RL, Schousboe A, Traynelis SF (2000) Control of GluRl AMPA receptor function by cAMP-dependent protein kinase. J Neurosci 20 89-102. 

Isaac, J.T., Ashby, M.C., and McBain, C.J., 2007. The role of the GluR2 subunit in AMPA receptor function and synaptic plasticity. Neuron. 54 859-871. 

Van Sickle BJ, Tietz El Selective enhancement of AMPA receptor-mediated function in hippocampal CAl nemons from chronic benzodiazepine-treated rats. Nemo-pharmacology 43 11—27, 2002... 

The recently developed GLUK5 selective compound LY382884 (47) is the first antagonist that is selective enough for kainate receptors over AMPA receptors to be used to study the functions of native KA receptors in the presence of intact AMPA receptor-mediated transmission. The use of LY382884 has uncovered a role for kainate receptors in the regulation of short- and long-term synaptic plasticity in the mossy-fiber pathway (49,77) as well as at thalamocortical synapses (87) (Fig. 3)... 

Anandamide has dual effects on NMDA receptor function. It reduces NMDA Ca2-i- currents, which is mediated by cannabinoid receptors and G-protein mechanisms (Hampson et al. 1998). However, anandamide potentiates NMDA currents due to a direct effect on the NMDA receptor itself. THC did not have the same effect. So anandamide appears to have at least one other CNS effect that is not through the cannabinoid receptors. THC also reduces AMPA/kainate activity, which is mediated by CBl receptors (Shen and Thayer 1999) (table 10.5). THC may in-... 

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