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

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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