6-Chloro-d,l-tryptophan, 4-chloro-3-hydroxyanthranilate and dexamethasone attenuate quinolinic acid accumulation in brain and blood following systemic immune activation

Kuniaki Saito, Sanford P. Markey, Melvyn P. Heyes

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Accumulations of the neurotoxin quinolinic acid (QUIN) occur in the brain and blood following immune activation and are attributed to increased metabolism of l-tryptophan through the kynurenine pathway. Systemic administration of 4-chloro-3-hydroxyanthranilate (an inhibitor of 3-hydroxyanthranilate-3,4-dioxygenase), 6-chloro-d,l-tryptophan (a substrate of the kynurenine pathway) and dexamethasone (an anti-inflammatory agent) attenuated the accumulation of QUIN in the brain and blood following systemic pokeweed mitogen administration to mice. 6-Chloro-d,l-tryptophan and dexamethasone also attenuated the increases in brain and lung indoleamine-2,3-dioxygenase activity and elevations in plasma l-kynurenine levels. We conclude that QUIN formation can be modified by drugs which act at different levels of the cascade of events that link immune stimulation to increased kynurenine pathway metabolism.

Original languageEnglish
Pages (from-to)211-215
Number of pages5
JournalNeuroscience Letters
Volume178
Issue number2
DOIs
Publication statusPublished - 12-09-1994
Externally publishedYes

Fingerprint

Quinolinic Acid
Kynurenine
Tryptophan
Dexamethasone
Brain
3-Hydroxyanthranilate 3,4-Dioxygenase
Indoleamine-Pyrrole 2,3,-Dioxygenase
Pokeweed Mitogens
Neurotoxins
Anti-Inflammatory Agents
Lung
4-chloro-3-hydroxyanthranilic acid
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

@article{0c6ee1523955499ba2f7ff78e54d6e2a,
title = "6-Chloro-d,l-tryptophan, 4-chloro-3-hydroxyanthranilate and dexamethasone attenuate quinolinic acid accumulation in brain and blood following systemic immune activation",
abstract = "Accumulations of the neurotoxin quinolinic acid (QUIN) occur in the brain and blood following immune activation and are attributed to increased metabolism of l-tryptophan through the kynurenine pathway. Systemic administration of 4-chloro-3-hydroxyanthranilate (an inhibitor of 3-hydroxyanthranilate-3,4-dioxygenase), 6-chloro-d,l-tryptophan (a substrate of the kynurenine pathway) and dexamethasone (an anti-inflammatory agent) attenuated the accumulation of QUIN in the brain and blood following systemic pokeweed mitogen administration to mice. 6-Chloro-d,l-tryptophan and dexamethasone also attenuated the increases in brain and lung indoleamine-2,3-dioxygenase activity and elevations in plasma l-kynurenine levels. We conclude that QUIN formation can be modified by drugs which act at different levels of the cascade of events that link immune stimulation to increased kynurenine pathway metabolism.",
author = "Kuniaki Saito and Markey, {Sanford P.} and Heyes, {Melvyn P.}",
year = "1994",
month = "9",
day = "12",
doi = "10.1016/0304-3940(94)90761-7",
language = "English",
volume = "178",
pages = "211--215",
journal = "Neuroscience Letters",
issn = "0304-3940",
publisher = "Elsevier Ireland Ltd",
number = "2",

}

6-Chloro-d,l-tryptophan, 4-chloro-3-hydroxyanthranilate and dexamethasone attenuate quinolinic acid accumulation in brain and blood following systemic immune activation. / Saito, Kuniaki; Markey, Sanford P.; Heyes, Melvyn P.

In: Neuroscience Letters, Vol. 178, No. 2, 12.09.1994, p. 211-215.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 6-Chloro-d,l-tryptophan, 4-chloro-3-hydroxyanthranilate and dexamethasone attenuate quinolinic acid accumulation in brain and blood following systemic immune activation

AU - Saito, Kuniaki

AU - Markey, Sanford P.

AU - Heyes, Melvyn P.

PY - 1994/9/12

Y1 - 1994/9/12

N2 - Accumulations of the neurotoxin quinolinic acid (QUIN) occur in the brain and blood following immune activation and are attributed to increased metabolism of l-tryptophan through the kynurenine pathway. Systemic administration of 4-chloro-3-hydroxyanthranilate (an inhibitor of 3-hydroxyanthranilate-3,4-dioxygenase), 6-chloro-d,l-tryptophan (a substrate of the kynurenine pathway) and dexamethasone (an anti-inflammatory agent) attenuated the accumulation of QUIN in the brain and blood following systemic pokeweed mitogen administration to mice. 6-Chloro-d,l-tryptophan and dexamethasone also attenuated the increases in brain and lung indoleamine-2,3-dioxygenase activity and elevations in plasma l-kynurenine levels. We conclude that QUIN formation can be modified by drugs which act at different levels of the cascade of events that link immune stimulation to increased kynurenine pathway metabolism.

AB - Accumulations of the neurotoxin quinolinic acid (QUIN) occur in the brain and blood following immune activation and are attributed to increased metabolism of l-tryptophan through the kynurenine pathway. Systemic administration of 4-chloro-3-hydroxyanthranilate (an inhibitor of 3-hydroxyanthranilate-3,4-dioxygenase), 6-chloro-d,l-tryptophan (a substrate of the kynurenine pathway) and dexamethasone (an anti-inflammatory agent) attenuated the accumulation of QUIN in the brain and blood following systemic pokeweed mitogen administration to mice. 6-Chloro-d,l-tryptophan and dexamethasone also attenuated the increases in brain and lung indoleamine-2,3-dioxygenase activity and elevations in plasma l-kynurenine levels. We conclude that QUIN formation can be modified by drugs which act at different levels of the cascade of events that link immune stimulation to increased kynurenine pathway metabolism.

UR - http://www.scopus.com/inward/record.url?scp=0027965458&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027965458&partnerID=8YFLogxK

U2 - 10.1016/0304-3940(94)90761-7

DO - 10.1016/0304-3940(94)90761-7

M3 - Article

C2 - 7824198

AN - SCOPUS:0027965458

VL - 178

SP - 211

EP - 215

JO - Neuroscience Letters

JF - Neuroscience Letters

SN - 0304-3940

IS - 2

ER -