関: kynurenate

WordNet

street name for lysergic acid diethylamide (同)back breaker, battery-acid, dose, dot, Elvis, loony toons, Lucy in the sky with diamonds, pane, superman, window pane, Zen
any of various water-soluble compounds having a sour taste and capable of turning litmus red and reacting with a base to form a salt
having the characteristics of an acid; "an acid reaction"

PrepTutorEJDIC

酸性の / 酸味のある,すっぱい(sour) / (言葉・態度などが)厳しい,しんらつな / 酸 / すっぱいもの / 《俗》=LSD

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/05/31 12:25:03」(JST)

wiki en

Kynurenic acid (KYNA) is a product of the normal metabolism of amino acid L-tryptophan. It has been shown that kynurenic acid possesses neuroactive activity. It acts as an antiexcitotoxic and anticonvulsant, most likely through acting as an antagonist at excitatory amino acid receptors. Because of this activity, it may influence important neurophysiological and neuropathological processes. As a result, kynurenic acid has been considered for use in therapy in certain neurobiological disorders. Conversely, increased levels of kynurenic acid have also been linked to certain pathological conditions.

Kynurenic acid was discovered in 1853 by the German chemist Justus von Liebig in dog urine, which it was apparently named after.^[1]

It is formed from L-kynurenine in a reaction catalyzed by the enzyme kynurenine—oxoglutarate transaminase.

Mechanism of action [edit]

KYNA has been proposed to act on four targets:

As an antagonist at ionotropic AMPA, NMDA and Kainate glutamate receptors in the concentration range of 0.1-2.5 mM^[2]
As a noncompetitive antagonist at the glycine site of the NMDA receptor.
As an antagonist of the α7 nicotinic acetylcholine receptor.^[3] However, recently (2011) direct recording of α7 nicotinic acetylcholine receptor currents in adult (noncultured) hippocampal interneurons by the Cooper laboratory ^[4] validated a 2009 study ^[5] that failed to find any blocking effect of kynurenic acid across a wide range of concentrations, thus suggesting that in noncultured, intact preparations from adult animals there is no effect of kynurenic acid on α7 nicotinic acetylcholine receptor currents ^[4] ^[5]
As a ligand for the orphan G protein-coupled receptor GPR35.^[6] Another tryptophan metabolite, 5-hydroxyindoleacetic acid exerts its effects via the orphan G protein-coupled receptor GPR35 ^[7]

Role in disease [edit]

High levels of kynurenic acid have been identified in patients suffering from tick-borne encephalitis, schizophrenia and HIV-related illnesses. In all these situations increased levels were associated with confusion and psychotic symptoms. Kynurenic acid acts in the brain as a glycine-site NMDAr antagonist, key in glutamatergic neurotransmission system, which is thought to be involved in the pathophysiology and pathogenesis of schizophrenia.

A kynurenic acid hypothesis of schizophrenia has been proposed in 2007,^[8]^[9] based on its action on midbrain dopamine activity and NMDArs, thus linking dopamine hypothesis of schizophrenia with the glutamate hypothesis of the disease.

High levels of kynurenic acid have been identified in human urine in certain metabolic disorders, such as marked pyridoxine deficiency and deficiency/absence of kynureninase.

When researchers decreased the levels of kynurenic acid in the brains of mice, the cognition was shown to improve markedly. ^[10]

References [edit]

^ Liebig, J., Uber Kynurensäure, Justus Liebigs Ann. Chem., 86: 125-126, 1853.
^ Elmslie KS, Yoshikami D. (1985) Effects of kynurenate on root potentials evoked by synaptic activity and amino acids in the frog spinal cord. Brain Res. Mar 25;330(2):265-72.
^ Hilmas, C., Pereira, EFR., Alkondon,M., Rassoulpour,A. Schwarcz,R., Albuquerque E.X.,(2001) The Brain Metabolite Kynurenic Acid Inhibits α7 Nicotinic Receptor Activity and Increases Non-α7 Nicotinic Receptor Expression: Physiopathological Implications. J. Neurosci 21(19):7463–7473.
^ ^a ^b Dobelis P., Varnell A., and Donald C. Cooper. Nicotinic α7 acetylcholine receptor-mediated currents are not modulated by the tryptophan metabolite kynurenic acid in adult hippocampal interneurons. (2011) Nature Precedings doi=10.1038/npre.2011.6277.1, http://www.neuro-cloud.net/nature-precedings/dobelis/
^ ^a ^b Mok MH, Fricker AC, Weil A, Kew JN (2009) Electrophysiological characterisation of the actions of kynurenic acid at ligand-gated ion channels. Neuropharmacology 57: 242-249.
^ Wang J, Simonavicius N, Wu X, Swaminath G, Reagan J, Tian H, Ling L (2006). "Kynurenic acid as a ligand for orphan G protein-coupled receptor GPR35". J. Biol. Chem. 281 (31): 22021–8. doi:10.1074/jbc.M603503200. PMID 16754668.
^ Grilli M, Raiteri L, Patti L, Parodi M, Robino F, Raiteri M, Marchi M (2006). "Modulation of the function of presynaptic α7 and non-α7 nicotinic receptors by the tryptophan metabolites, 5-hydroxyindole and kynurenate in mouse brain". Br. J. Pharmacol. 149 (6): 724–32. doi:10.1038/sj.bjp.0706914. PMC 2014664. PMID 17016503.
^ Erhardt S, Schwieler L, Nilsson L, Linderholm K, Engberg G (2007). "The kynurenic acid hypothesis of schizophrenia". Physiol. Behav. 92 (1–2): 203–9. doi:10.1016/j.physbeh.2007.05.025. PMID 17573079.
^ Erhardt S, Schwieler L, Engberg G (2003). "Kynurenic acid and schizophrenia". Adv. Exp. Med. Biol. 527: 155–65. PMID 15206728.
^ Robert Schwarcz; Elmer, Greg I; Bergeron, Richard; Albuquerque, Edson X; Guidetti, Paolo; Wu, Hui-Qiu; Schwarcz, Robert (2010). "Reduction of Endogenous Kynurenic Acid Formation Enhances Extracellular Glutamate, Hippocampal Plasticity, and Cognitive Behavior". Neuropsychopharmacology 35 (8): 1734–1742. doi:10.1038/npp.2010.39. PMC 3055476. PMID 20336058.

External links [edit]

Link found between TBE and schizophrenia - TheLocal.se, Sweden's news in English, 6 November 2007.

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 胎児の酸塩基の生理学 fetal acid base physiology
2. 神経管欠損予防のための葉酸 folic acid for prevention of neural tube defects
3. ポルフィリン症：概要 porphyrias an overview
4. 疾患予防におけるビタミン補給 vitamin supplementation in disease prevention
5. 胃酸分泌の生理学 physiology of gastric acid secretion

English Journal

KYNA analogue SZR72 modifies CFA-induced dural inflammation- regarding expression of pERK1/2 and IL-1β in the rat trigeminal ganglion.

Lukács M1,2, Warfvinge K3,4,5, Kruse LS6, Tajti J2, Fülöp F7, Toldi J8,9, Vécsei L2,9, Edvinsson L1,6.
The journal of headache and pain.J Headache Pain.2016 Dec;17(1):64. doi: 10.1186/s10194-016-0654-5. Epub 2016 Jul 5.
BACKGROUND: Neurogenic inflammation has for decades been considered an important part of migraine pathophysiology. In the present study, we asked the question if administration of a novel kynurenic acid analogue (SZR72), precursor of an excitotoxin antagonist and anti-inflammatory substance, can mod
PMID 27377707

Kynurenic acid and zaprinast induce analgesia by modulating HCN channels through GPR35 activation.

Resta F1, Masi A2, Sili M3, Laurino A4, Moroni F5, Mannaioni G6.
Neuropharmacology.Neuropharmacology.2016 Sep;108:136-43. doi: 10.1016/j.neuropharm.2016.04.038. Epub 2016 Apr 27.
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels have a key role in the control of cellular excitability. HCN2, a subgroup of the HCN family channels, are heavily expressed in small dorsal root ganglia (DRG) neurons and their activation seems to be important in the determination of
PMID 27131920

Glutamate in peripheral organs: Biology and pharmacology.

Du J1, Li XH2, Li YJ3.
European journal of pharmacology.Eur J Pharmacol.2016 Aug 5;784:42-48. doi: 10.1016/j.ejphar.2016.05.009. Epub 2016 May 7.
Glutamate is a versatile molecule existing in both the central nervous system and peripheral organs. Previous studies have mainly focussed on the biological effect of glutamate in the brain. Recently, abundant evidence has demonstrated that glutamate also participates in the regulation of physiopath
PMID 27164423

Japanese Journal

Prevention of Postoperative Fatigue Syndrome in Rat Model by Ginsenoside Rb1 via Down-Regulation of Inflammation along the NMDA Receptor Pathway in the Hippocampus

Chen Wei-Zhe,Liu Shu,Chen Fan-Feng [他],Zhou Chong-Jun,Yu Jian,Zhuang Cheng-Le,Shen Xian,Chen Bi-Cheng,Yu Zhen
Biological and Pharmaceutical Bulletin 38(2), 239-247, 2015
… Our results showed that POFS rats exhibited fatigue associated with an increased expression of inflammatory cytokines and NMDA receptor 1, higher (kynurenine)/(tryptophan) and (kynurenine)/(kynurenic acid) on postoperative days 1 and 3, and an increased expression of indoleamine 2,3-dioxygenase (IDO) on postoperative day 1. …
NAID 130004872253

Large Amounts of Picolinic Acid Are Lethal but Small Amounts Increase the Conversion of Tryptophan-Nicotinamide in Rats

SHIBATA Katsumi,FUKUWATARI Tsutomu
Journal of Nutritional Science and Vitaminology 60(5), 334-339, 2014
… Picolinic acid (PiA) is an endogenous metabolite of tryptophan that has been reported to possess a wide range of physiological actions. … Toxicity of PiA was higher than that of analogs such as nicotinic acid and quinolinic acid. … PiA did not affect the in vitro liver activities of quinolinic acid phosphoribosyltransferase or α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSDase, a Zn-dependent enzyme). …
NAID 130004773628

Time-Dependent Effects of L-Tryptophan Administration on Urinary Excretion of L-Tryptophan Metabolites

HIRATSUKA Chiaki,SANO Mitsue,FUKUWATARI Tsutomu,SHIBATA Katsumi
Journal of Nutritional Science and Vitaminology 60(4), 255-260, 2014
… The urinary excretion of L-Trp, kynurenic acid, 3-hydroxykynurenine, xanthurenic acid, 3-hydroxyanthranilic acid, quinolinic acid, N1-methylnicotinamide, N1-methyl-2-pyridone-5-carboxamide, and N1-methyl-4-pyridone-3-carboxamide increased in an L-Trp dose-dependent manner on day 7. …
NAID 130004695717

★リンクテーブル★

リンク元	「キヌレン酸」「kynurenate」
拡張検索	「5,7-dichlorokynurenic acid」

「キヌレン酸」

Kynurenic acid
	IUPAC name 4-hydroxyquinoline-2-carboxylic acid
	Other names Kinurenic acid, kynuronic acid, quinurenic acid, transtorine
Identifiers
CAS number	492-27-3
PubChem	3845
ChemSpider	3712
KEGG	C01717
ChEBI	CHEBI:18344
ChEMBL	CHEMBL299155
Jmol-3D images	Image 1
	SMILES O=C\2c1c(cccc1)NC(=C/2)/C(=O)O ;
	InChI InChI=1S/C10H7NO3/c12-9-5-8(10(13)14)11-7-4-2-1-3-6(7)9/h1-5H,(H,11,12)(H,13,14) ; Key: HCZHHEIFKROPDY-UHFFFAOYSA-N InChI=1/C10H7NO3/c12-9-5-8(10(13)14)11-7-4-2-1-3-6(7)9/h1-5H,(H,11,12)(H,13,14); Key: HCZHHEIFKROPDY-UHFFFAOYAN ;
Properties
Molecular formula	C10H7NO3
Molar mass	189.168 g/mol
Melting point	282.5°C
	(verify) (what is: /?); Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
	Infobox references