Ampa and kainate receptor agonist crystal structures glutamate binds. Medical search. Frequent questions

KARs are less understood than AMPA and NMDA receptors, the other ionotropic glutamate receptors. (wikipedia.org)
Ionotropic glutamate receptors (iGluRs) are the primary mediators of fast excitatory neurotransmission in the mammalian CNS where they are involved in learning and memory formation. (ku.dk)

Differences in the ligand binding pocket allow for the development of moderately subunit-selective kainate receptor agonists and antagonists. (wikipedia.org)
Whereas agonists induce a closure of domain D2 towards D1, antagonists stabilize an open conformation of the GluK1-LBD. (ku.dk)
Functional electrophysiological (TEVC) experiments indeed showed these compounds to be antagonists at cloned, homomeric KA receptors. (ku.dk)
Among these mGlu receptors, numerous ligands (agonists, antagonists, positive modulators or negative modulators) have been developed for the mGlu2/3 and mGlu5 receptors. (openmedicinalchemistryjournal.com)

Dopamine receptors are a class of metabotropic G protein-coupled receptors that are important in the central nervous system. (proteopedia.org)
Metabotropic glutamate receptors (mGlu receptors) have emerged as new therapeutic targets for psychiatric disorders, such as schizophrenia, depression and anxiety with their regulatory roles in glutamatergic transmissions. (openmedicinalchemistryjournal.com)

Postsynaptic kainate receptors are involved in excitatory neurotransmission. (wikipedia.org)
Glutamate is the major excitatory neurotransmitter in the brain. (openmedicinalchemistryjournal.com)

They were first identified as a distinct receptor type through their selective activation by the agonist kainate, a drug first isolated from the algae Digenea simplex. (wikipedia.org)
A few selective compounds that can discriminate between AMPA and kainate (KA) receptors are available. (ku.dk)
The structure and pharmacology will be valuable for design of new and more GluK3-selective quinoxalinedione analogues. (ku.dk)
To date, several ligands selective for each mGlu receptor have been synthesized, and pharmacological significances of these ligands have been demonstrated in animal models. (openmedicinalchemistryjournal.com)
These drugs are selective serotonin agonists, specifically acting at 5-hydroxytryptamine 1B/1D/1F (5-HT 1B/1D/1F ) receptors on intracranial blood vessels and sensory nerve endings. (medscape.com)
A selective agonist for serotonin 5-HT1 receptors, naratriptan has higher bioavailability and a longer half-life than sumatriptan, which may contribute to a lower rate of headache recurrences. (medscape.com)
A selective agonist for serotonin 5-HT1 receptors in cranial arteries, zolmitriptan suppresses the inflammation associated with migraine headaches. (medscape.com)
A selective 5-HT1B/1D receptor agonist, almotriptan results in cranial vessel constriction, inhibition of neuropeptide release, and reduced pain transmission in trigeminal pathways. (medscape.com)
Frovatriptan is a selective 5-HT1B/1D receptor agonist with a long half-life (26-30 h) and a low headache recurrence rate within 24 hours of taking the drug. (medscape.com)

The α-2 adrenergic receptor (A2AR) inhibits insulin or glucagons release. (proteopedia.org)
The β-1 adrenergic receptor (B1AR) increases cardiac output and secretion of rennin and ghrelin. (proteopedia.org)
The β-2 adrenergic receptor (B2AR) triggers many relaxation reactions. (proteopedia.org)
3D structures in Adrenergic receptor . (proteopedia.org)
Isoprenaline, see Beta-1 Adrenergic receptor , 2y03 . (proteopedia.org)
The human β2 adrenergic receptor bound to a G-protein ( 3sn6 ) is featured in a scene above, and additional structures are on the Adrenergic receptor page . (proteopedia.org)
For G s see Beta2 adrenergic receptor-Gs protein complex updated . (proteopedia.org)
In particular, we found correlations between three adrenergic receptor subtypes and alcohol deliveries which could indicate an involvement of stress in the choice to self-administer. (5dok.org)

Furthermore, the effects of calcium are observed at concentrations that are within the physiological range, suggesting that the ability of native GluRdelta2 to respond to ligand binding may be modulated by extracellular calcium. (ku.dk)
Here we report the pharmacology of a series of novel N1-substituted 2,3-quinoxalinediones, as well as the crystal structure of one compound (JP-10-7A) in the GluK1 ligand binding domain (GluK1-LBD) at 1.85 Å resolution. (ku.dk)
The GluK1 binding mode of the JP-10-7A 2,3-quinoxalinedione scaffold is similar to that of another published 2,3-quinoxalinedione ligand, (S)-2-amino-4-(2,3-dioxo-1,2,3,4-tetrahydroquinoxalin-6-yl)-butanoic acid (PDB-entry 4QF9), with the substituent in the N1-position pointing out of the binding pocket. (ku.dk)
It works as a postsynaptic neurotoxin binding to the receptor as an extracellular ligand by interacting with OH group leaving the acetylcholine channel open which releases ions used in creating an action potential. (proteopedia.org)

Presynaptic kainate receptors have been implicated in inhibitory neurotransmission by modulating release of the inhibitory neurotransmitter GABA through a presynaptic mechanism. (wikipedia.org)
The effect of BDNF was restricted to CB 1 Rs controlling GABA-mediated IPSCs (CB 1 R (GABA) ), whereas CB 1 Rs modulating glutamate transmission and GABA B receptors were not affected. (jneurosci.org)
The action of BDNF on CB 1 R (GABA) function was tyrosine kinase dependent and was complete even after receptor sensitization with cocaine or environmental manipulations activating the dopamine (DA)-dependent reward system. (jneurosci.org)
In mice lacking one copy of the BDNF gene ( BDNF +/− ), CB 1 R (GABA) responses were potentiated and were preserved from the action of haloperidol, a DA D 2 receptor (D 2 R) antagonist able to fully abolish CB 1 R (GABA) function in rewarded animals. (jneurosci.org)

There are five types of kainate receptor subunits, GluR5 (GRIK1), GluR6 (GRIK2), GluR7 (GRIK3), KA1 (GRIK4) and KA2 (GRIK5), which are similar to AMPA and NMDA receptor subunits and can be arranged in different ways to form a tetramer, a four subunit receptor. (wikipedia.org)
a receptor composed of both GluR5 and GluR6), however, KA1 and KA2 can only form functional receptors by combining with one of the GluR5-7 subunits. (wikipedia.org)
Since 2009 the kainate receptor subunits have been renamed to correspond with their gene name. (wikipedia.org)
Thus, there is an unmet need for Tool compounds with selectivity towards the remaining KA receptor subunits. (ku.dk)

Kainate receptors have a subtle role in synaptic plasticity, affecting the likelihood that the postsynaptic cell will fire in response to future stimulation. (wikipedia.org)
GluRdelta2 is a member of the iGluR family, but despite a prominent role in cerebellar synaptic plasticity, this receptor does not appear to function as an ion channel. (ku.dk)

Each KAR subunit begins with a 400-residue extracellular N-terminal domain, which plays a key role in assembly, followed by the first segment of the neurotransmitter-binding cleft, called S1. (wikipedia.org)
M2 turns into M3, another transmembrane segment which emerges on the extracellular face to complete the neurotransmitter binding site (a portion called S2). (wikipedia.org)

Kainate receptors, or kainic acid receptors (KARs), are ionotropic receptors that respond to the neurotransmitter glutamate. (wikipedia.org)

The convulsant kainic acid induces seizures, in part, by activation of kainate receptors containing the GluK2 subunit and also probably via AMPA receptors Activation of kainate receptors containing the GluK1 subunit can also induce seizures but deletion of this subunit does not reduce seizure susceptibility to kainate or in other seizure models. (wikipedia.org)

However, rise and decay times for postsynaptic potentials generated by KARs are slower than for AMPA postsynaptic potentials. (wikipedia.org)
Kainate receptors have both presynaptic and postsynaptic actions. (wikipedia.org)

cADPR mobilizes Ca 2+ from the endoplasmic reticulum by activation of ryanodine receptors , [4] a critical step in muscle contraction. (cloudfront.net)

These findings place GluRdelta2 among AMPA and kainate receptors, where the dimer interface is not only a biologically important site for functional regulation, but also an important target for exogenous and endogenous ligands that modulate receptor function. (ku.dk)
Among them, mGlu2/3 receptor agonists have been proven to be effective for treating schizophrenia and anxiety disorders in clinical studies, which may prove utilities of mGlu receptor ligands for the treatment of psychiatric disorders. (openmedicinalchemistryjournal.com)
This article reviews recent advances in development of each mGlu receptor ligands and their therapeutic potential. (openmedicinalchemistryjournal.com)

The receptor is a transmembrane pentameric glycoprotein. (proteopedia.org)

Our data suggest that calcium binding stabilizes the dimer interface formed between two agonist-binding domains and increases GluRdelta2(Lc) currents. (ku.dk)

The ion channel formed by kainate receptors is permeable to sodium and potassium ions. (wikipedia.org)

Activator of protein kinase A (cyclic AMP agonist). (biolog.de)

The adrenergic receptors are metabolic G protein-coupled receptors. (proteopedia.org)

Domain opening of GluK1-LBD with JP-10-7A bound (compared to glutamate bound GluK1-LBD PDB-entry 2F36, molA) is approximately 30°, which is consistent with an antagonist binding mode. (ku.dk)
L-phenylalanine is a competitive antagonist for the glycine- and glutamate-binding sites of N-methyl-D-aspartate receptors (NMDARs) (KB of 573 μM ) and non-NMDARs, respectively. (medchemexpress.com)

This segment, termed the "p loop," determines the calcium permeability of the receptor. (wikipedia.org)
Taking advantage of known crystal structures and spontaneously active GluRdelta2 receptors containing the lurcher mutation (GluRdelta2(Lc)), we investigated the mechanism by which calcium and d-serine regulate the activity of GluRdelta2(Lc). (ku.dk)
Calcium binding by synaptotagmins releases this fusion clamp and triggers fast SV exocytosis. (bvsalud.org)

Here, we addressed the functional interplay between BDNF and cannabinoid CB 1 receptors (CB 1 Rs) in the striatum, a brain area in which both BDNF and CB 1 s play a role in the emotional consequences of stress and of rewarding experiences. (jneurosci.org)

One of the larger connections and roles that kainate receptors have been shown to have is to several neurological diseases and conditions. (wikipedia.org)

However, within the KA receptor family (GluK1-5) only compounds with selectivity towards GluK1 exist [1]. (ku.dk)

The data further suggest that d-serine binding induces rearrangements at the dimer interface to diminish GluRdelta2(Lc) currents by a mechanism that resembles desensitization at AMPA and kainate receptors. (ku.dk)

The proteins have been shown to pace the receptors and help explain KAR's role in maturation of neural circuits during development. (wikipedia.org)
M1, M3, M5 receptors are coupled with G q proteins, while M2 and M4 receptors are coupled with G i/o proteins. (proteopedia.org)

There must be 5 molecules of cobra toxin (red) to block the receptor (blue) as each molecule binds with an individual alpha chain on the acetylcholine receptor. (proteopedia.org)

The single channel conductance of kainate receptor channels is similar to that of AMPA channels, at about 20 pS. (wikipedia.org)
cADPR also acts as an agonist for the TRPM2 channel, but less potently than ADPR . (cloudfront.net)

They have a somewhat more limited distribution in the brain than AMPA and NMDA receptors, and their function is less well defined. (wikipedia.org)

The D3 receptor is a part of the D2-like family. (proteopedia.org)

Group I mGlu receptors include mGlu1 and mGlu5 that are coupled to phospholipase C, while both group II mGlu receptors (mGlu2 and mGlu3) and group III mGlu receptors (mGlu4, mGlu6, mGlu7, and mGlu8) are negatively coupled to adenylyl cyclase activity. (openmedicinalchemistryjournal.com)

Recent investigation through voltage clamping has shown that kainate receptors have more than just an ionotropic (or directly changing a membrane's conductivity) role in neurons. (wikipedia.org)

Unlike AMPA receptors, kainate receptors play only a minor role in signaling at synapses. (wikipedia.org)

Anatomy15

Organisms6

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Chemicals and Drugs89

Analytical, Diagnostic and Therapeutic Techniques and Equipment15

Psychiatry and Psychology1

Phenomena and Processes45

Disciplines and Occupations2

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Ionotropic glutamate receptors2

Antagonists4

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