Receptor 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. 

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. 

The role of the kainate receptor system in the brain is at an early stage since there are as yet few pharmacological tools to study its function. However, mutations in the kainate receptor genes have been made in mice and there is a GluR6 kainate receptor knock-out mouse. Kainate binding is absent in areas of the brain which normally have high levels such as the hippocampus. Here, in normal animals kainate receptors mediate a postsynaptic current which is absent in the GluR6 knock-out mouse. The mice have... 

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

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. 

PCP is not acting as a competitive inhibitor at the NMDA receptor thus, PCP and NMDA probably do not share a common recognition site. Examination of the effect of PCP on NMDA-induced DA release (figure 1, lower panel) tends to support this conclusion, but is compromised somewhat by the slightly nonparallel shift produced by 2-APV. This may be due to the fact that NMDA may partially activate quisqualate and kainate receptors on those neurons that are not antagonized by 2-APV. 

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. 

TABLE 3.2 Subunits of the 3TM NMDA Receptors Superfamily AMPA Receptors Kainate Receptors Orphan Receptors... 

The kainate receptors are composed of subunits from the GluR5-GluR7 class and the KA1-KA2 class of subunits. Homomeric receptors of the former class generate functional receptors and bind kainate with an affinity of 50 to 100 nM. KA1 or KA2 do not generate functional channels, but the receptors bind kainate with an affinity of 5 to 10 nM. Homomeric GluR6 and KA2 receptors are neither activated by AMPA, nor do they bind AMPA. Interestingly, when they are co-expressed, heteromeric receptors respond to AMPA. 

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