Last update 01 Nov 2024

GluK5

Last update 01 Nov 2024

Basic Info

Synonyms

EAA2, Excitatory amino acid receptor 2, GluK5

+ [7]

Introduction

Receptor for glutamate. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. This receptor binds kainate > quisqualate > domoate > L-glutamate >> AMPA >> NMDA = 1S,3R-ACPD.

Drugs associated with GluK5

NS3763

Target

GluK5

Mechanism

GluK5 antagonists

Active Org.

Neurosearch

Originator Org.

Neurosearch

Active Indication

Epilepsy [+2]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

LY-466195

Target

GluK5 x Kainate receptor

Mechanism

GluK5 antagonists [+1]

Active Org.

Eli Lilly & Co. [+1]

Originator Org.

Eli Lilly & Co.

Active Indication

Migraine Disorders

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

LBG20304

Target

GluK5

Mechanism

GluK5 agonists

Active Org.

University of Copenhagen

Originator Org.

University of Copenhagen

Active Indication-

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with GluK5

100 Translational Medicine associated with GluK5

0 Patents (Medical) associated with GluK5

270

Literatures (Medical) associated with GluK5

19 Sep 2024·Cells

Cannabinol (CBN) Influences the Ion Channels and Synaptic-Related Genes in NSC-34 Cell Line: A Transcriptomic Study.

Article

Author: Trainito, Alessandra ; Gugliandolo, Agnese ; D'Angiolini, Simone ; Salamone, Stefano ; Muscarà, Claudia ; Chiricosta, Luigi ; Mazzon, Emanuela ; Pollastro, Federica

Neurological disorders such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, and schizophrenia are associated with altered neuronal excitability, resulting from dysfunctions in the molecular architecture and physiological regulation of ion channels and synaptic transmission. Ion channels and synapses are regarded as suitable therapeutic targets in modern pharmacology. Cannabinoids have received great attention as an original therapeutic approach for their effects on human health due to their ability to modulate the neurotransmitter release through interaction with the endocannabinoid system. In our study, we explored the effect of cannabinol (CBN) through next-generation sequencing analysis of NSC-34 cell physiology. Our findings revealed that CBN strongly influences the ontologies related to ion channels and synapse activity at all doses tested. Specifically, the genes coding for calcium and potassium voltage-gated channel subunits, and the glutamatergic and GABAergic receptors (Cacna1b, Cacna1h, Cacng8, Kcnc3, Kcnd1, Kcnd2, Kcnj4, Grik5, Grik1, Slc17a7, Gabra5), were up-regulated. Conversely, the genes involved into serotoninergic and cholinergic pathways (Htr3a, Htr3b, Htr1b, Chrna3, Chrnb2, Chrnb4), were down-regulated. These findings highlight the influence of CBN in the expression of genes involved into ion influx and synaptic transmission.

22 Aug 2024·Journal of Medicinal Chemistry

Domoic Acid as a Lead for the Discovery of the First Selective Ligand for Kainate Receptor Subtype 5 (GluK5)

Article

Author: Buschbom-Helmke, Silke ; Miguez-Cabello, Federico ; Pickering, Darryl S. ; Bunch, Lennart ; Carta, Mario ; Wang, Pengfei ; Bowie, Derek ; Nielsen, Birgitte ; Jørgensen, Flemming Steen ; Mulle, Christophe ; Viotti, Julio S. ; Alcaide, Anna

Twenty-one simplified analogues of the natural product domoic acid were designed, synthesized, and then characterized at homomeric kainic acid (KA) receptors (GluK1-3,5). LBG20304 displays a high affinity for homomeric GluK5 receptors (IC₅₀ = 432 nM) with a >40-fold selectivity over homomeric GluK1-3 subtypes and ≫100-fold selectivity over native AMPA and N-methyl d-aspartate receptors. Functional studies of LBG20304 on heteromeric GluK2/5 receptors show no agonist or antagonist functional response at 10 μM, while a concentration of 100 μM at neuronal slices (rat) shows low agonist activity. A molecular dynamics simulation of LBG20304, in a homology model of GluK5, suggests specific interactions with the GluK5 receptor and an occluded ligand binding domain, which is translated to agonist or partial agonist activity. LBG20304 is a new compound for the study of the role and function of the KA receptors with the aim of understanding the involvement of these receptors in health and disease.

01 Oct 2023·DNA and cell biology

Altered G-Protein Transduction Protein Gene Expression in the Testis of Infertile Patients with Nonobstructive Azoospermia.

Article

Author: Azizi, Hossein ; Skutella, Thomas ; Hashemi Karoii, Danial

Recent studies have shown that several members of the G-protein-coupled receptors (GPCR) superfamily play crucial roles in the maintenance of ion-water homeostasis of the sperm and Sertoli cells, development of the germ cells, formation of the blood barrier, and maturation of sperm. The GPCR, guanyl-nucleotide exchange factor, membrane traffic protein, and small GTPase genes were analyzed by microarray and bioinformatics (3513 sperm and Sertoli cell genes). In the microarray analyses of three human cases with different nonobstructive azoospermia sperm, the expression of GOLGA8IP, OR2AT4, PHKA1, A2M, OR56A1, SEMA3G, LRRC17, APP, ARHGAP33, RABGEF1, NPY2R, GHRHR, LTB4R2, GRIK5, OR6K6, NAPG, OR6C65, VPS35, FPR3, and ARL4A was upregulated, while expression of MARS, SIRPG, OGFR, GPR150, LRRK1, and NGEF was downregulated. There was an increase in GBP3, GBP3, TNF, TGFB3, and CLTC expression in the Sertoli cells of three human cases with NOA, whereas expression of PAQR4, RRAGD, RAC2, SERPINB8, IRPB1, MRGPRF, RASA2, SIRPG, RGS2, RAP2A, RAB2B, ARL17, SERINC4, XIAP, DENND4C, ANKRA2, CSTA, STX18, and SNAP23 were downregulated. A combined analysis of Enrich Shiny Gene Ontology (GO), STRING, and Cytoscape was used to predict proteins' molecular interactions and then to recognize master pathways. Functional enrichment analysis showed that the biological process (BP), regulation of protein metabolic process, regulation of small GTPase-mediated signal transduction were significantly expressed in up-/downregulated differentially expressed genes (DEGs) in sperm. In molecular function (MF) experiments of DEGs that were up-/downregulated, it was found that GPCR activity, guanyl ribonucleotide binding, GTPase activity and nucleoside-triphosphatase activity were overexpressed. An analysis of GO enrichment findings of Sertoli cells showed BP and MF to be common DEGs. When these gene mutations have been validated, they can be used to create new GPCR antagonists or agonists that are receptor-selective.

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