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a(CHEBI:"kynurenic acid")

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Entity

Name
kynurenic acid
Namespace
chebi
Namespace Version
20180906
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/chebi-names.belns

Appears in Networks 1

albuquerque2009 v1.0.0

This file encodes the article Mammalian Nicotinic Acetylcholine Receptors: From Structure to Function by Albuquerque et al, 2009

In-Edges 8

a(CHEBI:"L-kynurenine") increases a(CHEBI:"kynurenic acid") View Subject | View Object

KYNA is formed enzymatically by the irreversible transamination of L-kynurenine, a major peripheral tryptophan metabolite with ready access to the brain. Immunohistochemical and lesion studies demonstrated that cerebral KYNA synthesis takes place almost exclusively in astrocytes (129, 187, 199). PubMed:19126755

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Astrocytes
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a(CHEBI:kynurenine) increases a(CHEBI:"kynurenic acid") View Subject | View Object

In the normal brain, 70% of KYNA formation is catalyzed by KAT II, one of the three cerebral KATs (199, 200). Systemic treatment of rats and mice with kynurenine leads to an elevation of brain levels of several neuroactive intermediates, including KYNA, the free radical generator 3-hydroxykynurenine, and the excitotoxic quinolinic acid (419). PubMed:19126755

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a(MESH:Astrocytes) increases a(CHEBI:"kynurenic acid") View Subject | View Object

Of note is that in both of these catastrophic disorders, reduced nAChR activity/expression is accompanied by increased levels of kynurenic acid (KYNA), a tryptophan metabolite that in the brain is primarily produced and released by astrocytes (244, 419). PubMed:19126755

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a(MESH:Neurons) regulates a(CHEBI:"kynurenic acid") View Subject | View Object

Interestingly, astrocytic KYNA production is regulated by neuronal activity (187) and cellular energy metabolism (213). This dependence of extracellular KYNA concentrations on the functional interplay between neurons and astrocytes is in line with the postulated neuromodulatory role of KYNA (418) and adds to the complexity of the neurochemical networks in the brain. PubMed:19126755

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a(MESH:Probenecid) decreases a(CHEBI:"kynurenic acid") View Subject | View Object

Because of the absence of reuptake or degradation mechanisms, subsequent KYNA removal is accomplished exclusively by probenecid-sensitive brain efflux (330, 473). PubMed:19126755

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bp(GO:"energy homeostasis") regulates a(CHEBI:"kynurenic acid") View Subject | View Object

Interestingly, astrocytic KYNA production is regulated by neuronal activity (187) and cellular energy metabolism (213). This dependence of extracellular KYNA concentrations on the functional interplay between neurons and astrocytes is in line with the postulated neuromodulatory role of KYNA (418) and adds to the complexity of the neurochemical networks in the brain. PubMed:19126755

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act(p(HGNCGENEFAMILY:"Cholinergic receptors nicotinic subunits")) negativeCorrelation a(CHEBI:"kynurenic acid") View Subject | View Object

Of note is that in both of these catastrophic disorders, reduced nAChR activity/expression is accompanied by increased levels of kynurenic acid (KYNA), a tryptophan metabolite that in the brain is primarily produced and released by astrocytes (244, 419). PubMed:19126755

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act(p(HGNC:AADAT), ma(cat)) increases a(CHEBI:"kynurenic acid") View Subject | View Object

In the normal brain, 70% of KYNA formation is catalyzed by KAT II, one of the three cerebral KATs (199, 200). Systemic treatment of rats and mice with kynurenine leads to an elevation of brain levels of several neuroactive intermediates, including KYNA, the free radical generator 3-hydroxykynurenine, and the excitotoxic quinolinic acid (419). PubMed:19126755

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Out-Edges 12

a(CHEBI:"kynurenic acid") negativeCorrelation act(p(HGNCGENEFAMILY:"Cholinergic receptors nicotinic subunits")) View Subject | View Object

Of note is that in both of these catastrophic disorders, reduced nAChR activity/expression is accompanied by increased levels of kynurenic acid (KYNA), a tryptophan metabolite that in the brain is primarily produced and released by astrocytes (244, 419). PubMed:19126755

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a(CHEBI:"kynurenic acid") decreases act(p(HGNCGENEFAMILY:"Glutamate ionotropic receptor NMDA type subunits")) View Subject | View Object

The neuroactive properties of KYNA have long been attributed to the inhibition of NMDA receptors (329). Electrophysiological studies, however, have demonstrated that physiologically relevant concentrations of KYNA block alpha7 nAChR activity noncompetitively and voltage independently (210). PubMed:19126755

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a(CHEBI:"kynurenic acid") decreases act(p(HGNC:CHRNA7)) View Subject | View Object

The neuroactive properties of KYNA have long been attributed to the inhibition of NMDA receptors (329). Electrophysiological studies, however, have demonstrated that physiologically relevant concentrations of KYNA block alpha7 nAChR activity noncompetitively and voltage independently (210). PubMed:19126755

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a(CHEBI:"kynurenic acid") regulates act(p(HGNC:CHRNA7)) View Subject | View Object

This constituted the first evidence that in the hippocampus endogenous levels of KYNA are sufficient to directly modulate the activity of alpha7 nAChRs, but not that of NMDA receptors (31). PubMed:19126755

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Hippocampus
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Review

a(CHEBI:"kynurenic acid") regulates act(p(HGNC:CHRNA7)) View Subject | View Object

Acting as an endogenous regulator of the alpha7 nAChR activity, astrocyte-derived KYNA can modulate synaptic transmission, synaptic plasticity, neuronal viability, and neuronal connectivity in different areas of the brain (Fig. 8). PubMed:19126755

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a(CHEBI:"kynurenic acid") decreases act(p(HGNC:CHRNA7)) View Subject | View Object

As illustrated in Figure 8, KYNA-induced reduction of extracellular dopamine levels can be explained by the inhibition of tonically active alpha7 nAChRs in the dopaminergic neurons within the VTA and/or in cortical glutamatergic terminals that synapse onto striatal neurons. VTA dopaminergic neurons represent the major dopaminergic input to the nucleus accumbens. PubMed:19126755

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MeSH
Dopaminergic Neurons
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a(CHEBI:"kynurenic acid") decreases act(p(HGNC:CHRNA7)) View Subject | View Object

Chronic alpha7 nAChR inhibition in the hippocampus by elevated levels of KYNA can contribute to auditory gating deficits, which appear to be associated with the development of schizophrenia (156). It is also feasible that KYNAinduced inhibition of alpha7 nAChRs contributes to the cognitive impairment observed in patients with AD and schizophrenia (273). PubMed:19126755

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MeSH
Hippocampus
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Review

a(CHEBI:"kynurenic acid") decreases act(p(MGI:Chrna7, loc(MESH:Interneurons))) View Subject | View Object

Mice with a null mutation in the gene that encodes KAT II became a unique tool to resolve this issue (31, 410, 516). Low levels of KYNA in these mutant mice lead to alpha7 nAChR disinhibition in hippocampal CA1 SR interneurons, thereby increasing the activity of GABAergic interneurons impinging onto CA1 pyramidal neurons (31) PubMed:19126755

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MeSH
CA1 Region, Hippocampal
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a(CHEBI:"kynurenic acid") regulates bp(MESH:"Neuronal Plasticity") View Subject | View Object

Acting as an endogenous regulator of the alpha7 nAChR activity, astrocyte-derived KYNA can modulate synaptic transmission, synaptic plasticity, neuronal viability, and neuronal connectivity in different areas of the brain (Fig. 8). PubMed:19126755

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a(CHEBI:"kynurenic acid") regulates bp(GO:"synaptic transmission, cholinergic") View Subject | View Object

Acting as an endogenous regulator of the alpha7 nAChR activity, astrocyte-derived KYNA can modulate synaptic transmission, synaptic plasticity, neuronal viability, and neuronal connectivity in different areas of the brain (Fig. 8). PubMed:19126755

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a(CHEBI:"kynurenic acid") regulates path(MESH:"Cell Survival") View Subject | View Object

Acting as an endogenous regulator of the alpha7 nAChR activity, astrocyte-derived KYNA can modulate synaptic transmission, synaptic plasticity, neuronal viability, and neuronal connectivity in different areas of the brain (Fig. 8). PubMed:19126755

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a(CHEBI:"kynurenic acid") decreases a(CHEBI:dopamine, loc(GO:"extracellular region")) View Subject | View Object

Activation of alpha7 nAChRs is known to contribute to the regulation of extracellular dopamine levels in the rat striatum (81). Application via microdialysis of KYNA or alpha-BGT to the rat striatum significantly reduces the extracellular levels of dopamine, and the magnitude of the effect of either antagonist alone is comparable to that of both antagonists together (285). PubMed:19126755

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MeSH
Corpus Striatum
Text Location
Review

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