Kainate

Glutamate receptor. agonists ( excitotoxins ) glutamate, kainate,... 

Whereas the role of AMPA and NMDA receptors in fast synaptic transmission is well characterized, only few examples demonstrating synaptic responses due to kainate receptor activation are known so far. 

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. 

Lerma J (1999) Kainate receptors, chapter 8 Ionotropic glutamate receptors in the CNS. Springer Verlag... 

Kainate receptors are a subtype of ionotropic glutamate receptors that are permeable to Na+, K+ and Ca2+ ions. 

Transduction mechanism Inhibition of adenylyl cyclase stimulation of tyrosine phosphatase activity stimulation of MAP kinase activity activation of ERK inhibition of Ca2+ channel activation stimulation of Na+/H+ exchanger stimulation of AM PA/kainate glutamate channels Inhibition of forskol in-stimulated adenylyl cyclase activation of phos-phoinositide metabolism stimulation of tyrosine phosphatase activity inhibition of Ca2+ channel activation activation of K+ channel inhibition of AM PA/ kainate glutamate channels inhibition of MAP kinase activity inhibition of ERK stimulation of SHP-1 and SHP-2 Inhibition of adenylyl cyclase stimulation of phosphoinositide metabolism stimulation of tyrosine phosphatase activation of K+ channel inhibi-tion/stimulation of MAP kinase activity induction of p53 and Bax Inhibition of adenylyl cyclase stimulation of MAP kinase stimulation of p38 activation of tyrosine phosphatase stimulation of K+ channels and phospholipase A2 Inhibition of adenylyl cyclase activation/ inhibition of phosphoinositide metabolism inhibition of Ca2+ influx activation of K+ channels inhibition of MAP kinase stimulation of tyrosine phosphatase... 

Kainate Receptor Kallidin, Lysyl-Bradykinin Kallikrein KCNQ-Channels KCOs... 

Carta M, Ariwodola OJ, Weiner J L, et al Alcohol potently inhibits the kainate receptor-dependent excitatory drive of hippocampal interneurons. Proc Natl Acad Sci U SA 100 6813-6818, 2003... 

Gray A, Allison C, Pratt JA A role for AMPA/kainate receptors in conditioned place preference induced by diazepam in the rat. Neurosci Lett 268 127-130, 1999... 

Kainate receptors may be formed by homomeric combination of GluRS, GluR6 or GluR7 or by heteromeric combination of any of GluRS 7 with the kainate binding proteins, KAl or KA2. KAl and KA2 do not form functional homomeiic receptors. 

Unlike other transmitter systems, there are no obvious meehanisms for dampening glutamate release. Presynaptic autoreceptors for glutamate are mostly of the kainate type (see below) and appear to act as positive rather than negative influenees on further release of the amino acid. Although poorly characterised at present, inhibitory autoreceptors of the metabotropic type of receptors may act to inhibit release of glutamate. 

Non-NMDA ionotropic glutamate receptors (the majority sodium channel containing) can be subdivided into a-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) (comprising cloned subunits GluRl ) and kainate (GluR5-7, KAl-2) preferring receptors, with native receptors most likely to comprise either homo- or heteromeric pentamers of these subunits. 

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