Glutamate kainate

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

AMPA provides an interesting test case because it displays a binding mode that differs from those of, e.g., glutamate, kainate, and 2-methyltetrazolyl AMPA at iGluR2. 

N on-NMDA-Glu-R (K-R) interaction — alleviates neurotoxicity of Glutamate kainate (but not of NMDA)... 

Glutamate, kainate Glutamate, AMPA quisqualate Extracellular ATP, a,p-methyleneATP (<10 pM)... 

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... 

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. 

Dingledine, R et al. (1999) The glutamate receptor ion channels. Pharmacol. Rev. 51 7-61. Frerking, M and Nicoll, RA (2000) Synaptic kainate receptors. Curr. Opin. Neurobiol. 10 342-351. Gegelashvili, G and Schousboe, A (1997) High affinity glutamate transporters regulation of expression and activity. Mol. Pharmacol. 52 6-15. 

Hollman, M and Heinemann, S (1994) Cloned glutamate receptors. Arm. Rev. Neurosci. 17 31-108. Lerma, J (1997) Kainate reveals its targets. Neuron 19 1155-1158. 

FIGURE 3.8 Kainate and AMPA activate different current responses in the different classes of kainate and AMPA receptors (a) the AMPA receptor, GluRl (b) and (c) kainate receptors (d) glutamate + glycine activation of the NMDA receptor. The current response is characterized by a slow onset and offset compared to the kainate and AMPA receptors. 

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