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Jane, David E.; Lodge, David; Collingridge, Graham L.
Neuropharmacology, January 2009, 2009-Jan, 2009-01-00, 20090101, Letnik: 56, Številka: 1Journal Article
Compared to the other glutamate receptors, progress in the understanding of the functions of kainate receptors (KARs) has lagged behind, due mainly to the relative lack of specific pharmacological tools. Over the last decade subunit selective agonists (e.g. ATPA and 5-iodowillardiine) and orthosteric (e.g. LY382884 and ACET) and allosteric antagonists for KARs that contain GluK1 (GluR5) subunits have been developed. However, no selective ligands for the other KAR subunits have been identified. The use of GluK1 antagonists has enabled several functions of KARs, that contain this subunit, to be identified. Thus, KARs have been shown to regulate excitatory and inhibitory synaptic transmission. In the case of the regulation of l-glutamate release, they can function as facilitatory autoreceptors or inhibitory autoreceptors during repetitive synaptic activation and can respond to ambient levels of l-glutamate to provide a tonic regulation of l-glutamate release. KARs also contribute a component of excitatory synaptic transmission at certain synapses. They can also act as triggers for both long-term potentiation (LTP) and long-term depression (LTD) and rapid alterations in their trafficking can result in altered synaptic transmission during both synaptic plasticity and neuronal development. KARs also contribute to synchronised rhythmic activity in the brain and are involved in forms of learning and memory. With respect to therapeutic indications, antagonists for GluK1 have shown positive activity in animal models of pain, migraine, epilepsy, stroke and anxiety. This potential has now been confirmed in dental pain and migraine in initial studies in man.
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