AMPA and kainate receptors

Hippocampus Cerebellum Spinal cord Caudate putamen Retina 

Dentate granule CAl pyramidal CAS pyramidal Purkinje Granule cell Bergmann Motor Medium spiny Cholinergic Retinal OFF-bipolar 

GluR-Ci.o GluR-Cj,o GluR-C, GluR-Ci GluR-Ci, GluR-Ci (lower)  

GluR-Do GluR-Do GluR-Do GluR-Di GluR-Di GluR-Do (lower) GluR-D  

Flip and flop splice forms of AMPA receptor subunits are indicated by i and o suffixes. Modified from Wisden and Seeburg (1993b). Glutamate receptor subunit mRNAs in selected adult rat CNS cells. 

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Some AMPA and kainate receptors are calcium permeable. Some of the antagonist structures are shown in Fig. 10.4. 

AMPA and kainate receptors are both blocked by quinoxalinediones but have different desensitization pharmacologies. AMPAreceptors are widespread throughout the CNS they serve as receptors for fast excitatory synaptic transmission mediated by glutamate. AMPA receptor subunits are GluRl-GluR4, kainate receptor... 

AMPA receptors desensitize within milliseconds upon exposure to AMPA, and kainate receptors likewise upon exposure to kainate. AMPA and kainate receptors can be securely distinguished from one another by their response to two drugs, cyclothiazide and the lectin concanavalin A [10], Cyclothiazide relieves AMPA receptor desensitization without affecting kainate receptors. 

Selective agonist binding of AMPA and kainate receptors. P21, Biomolecular Interactions, Molecular Graphics and Modelling Society, Bristol UK, 3-5 April. 

Jane, D. E., Hoo, K., Kamboj, R Deverill, M Bleakman, D and Mandelzys, A. Synthesis of willardiine and 6-azawillardiine analogues pharmacological characterization on cloned homomeric human AMPA and kainate receptor subtypes../. Med. Chem. 40, 3645-3650. 

The quinoxalinedione derivatives 6-cyano-7-nitroquinoxaline (CNQX), 6,7-dinitro-quinoxaline-2,3-dione (DNQX), and 2,3-dioxo-6-nitro-l,2,3,4-tetrahydrobenzo[f]quinox-aline-7-sulphonamide (NBQX) are potent competitive antagonists of AMPA and kainate receptors. Of these, NBQX shows the most functional selectivity (approximately threefold) for AMPA over KA receptors (45), and has been used in low concentrations (1 pM) to isolate kainate currents in hippocampal interneurons (46). 

Bleakman, D. and Lodge, D. (1998) Neuropharmacology of AMPA and kainate receptors. 

Bettler, B. and Mulle, C. (1995) Review neurotransmitter receptors. II. AMPA and kainate receptors. Neuropharmacology 34,123-139. 

Hirbec, H Francis, J. C Lauri, S. E et al. (2003) Rapid and differential regulation of AMPA and Kainate receptors at hippocampal mossy fibre synapses by PICK1 and GRIP. Neuron 37,625-638. 

The excitatoiy amino acids (EAA), glutamate and aspartate, are the principal excitatory neurotransmitters in the brain. They are released by neurons in several distinct anatomical pathways, such as corticofugal projections, but their distribution is practically ubiquitous in the central nervous system. There are both metabotropic and ionotropic EAA receptors. The metabotropic receptors bind glutamate and are labeled mGluRl to mGluRB. They are coupled via G-proteins to phosphoinositide hydrolysis, phospholipase D, and cAMP production. Ionotropic EAA receptors have been divided into three subtypes /V-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid (AMPA), and kainate receptors (Nakanishi 1992). 

However, it is not the only mechanism, because drugs that do not work at NMDA receptors can impair memory (e.g., benzodiazepines). Other EAA receptors include the ionotropic AMPA and kainate receptors, and the metabotropic glutamate receptors (mGluR). 

Neurochemicals distinguish the reductionistic-type sensory pathways from the integrative-type action circuitry. Sensory pathways commonly use the excitatory neurotransmitters glutamate or aspartate at virtually every relay. Most actions along these pathways are mediated by the fast acting glutamate receptors ofthe iontropicvariety (i.e., AMPA and kainate receptors). Acetylcholine is... 

There are three types of ionotropic glutamate receptors NMDA, a-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA), and kainate receptors (Fig. 1). Each is principally activated by the agonist bearing its name and is permeable to cationic flux hence, their activation results in membrane depolarization. Ionotropic glutamate receptors were originally classified based on three selective, synthetic agonists quisqualate, kainate and NMDA. After the discovery of metabotropic receptors, it became clear that quisqualate also interacts with them. Since that time, quisqualate-sensitive ionotropic receptors have been classified by the more selective agonist AMPA. 

The role of non-NMDA receptor modulators in pain is not as clear as the role of NMDA receptors, but there is evidence to indicate that AMPA and kainate receptors may be involved in nociceptive processing. 

Weston M. C., Gertler C., Mayer M. L., and Rosenmund C. (2006). Interdomain interactions in AMPA and kainate receptors regulate affinity for glutamate. J. Neurosci. 26 7650-7658. 

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