A mechanism for increased quinolinic acid formation following acute systemic immune stimulation

Kuniaki Saito, J. S. Crowley, S. P. Markey, M. P. Heyes

Research output: Contribution to journalArticle

164 Citations (Scopus)

Abstract

Mechanisms for increased levels of quinolinic acid (QUIN) following systemic immune stimulation were investigated. In gerbils, systemic administration of pokeweed mitogen (PWM) increased plasma and cerebrospinal fluid QUIN levels, while plasma kynurenic acid levels were decreased and cerebrospinal fluid kynurenic acid levels were unchanged. PWM also increased the QUIN concentrations of brain and systemic tissues. In slices of spleen, lung, liver, duodenum, and kidney, PWM caused marked increases in [13C6]QUIN formation from L-[13C6]tryptophan (but not from [13C6]anthranilic acid). PWM also increased QUIN excretion in the urine and enhanced the formation and excretion of [13C6]QUIN following an intraperitoneal injection of L-[13C6]tryptophan. Indoleamine-2,3- dioxygenase activity was increased in the brain, kidney, lung, spleen, and duodenum while hepatic L-tryptophan-2,3-dioxygenase activity was reduced, data consistent with in vitro L-kynurenine formation from L-tryptophan. Kynurenine-3-hydroxylase activity was increased in the duodenum, lung, and spleen, but not in the brain, kidney, or liver. Kynureninase activity was increased in the brain, lung, and duodenum, but not in the spleen, kidney, or liver. 3-Hydroxyanthranilate-3,4-dioxygenase activity was unchanged in the brain, lung, and liver. No change in kynurenine aminotransferase activity was observed in the brain or lung, while liver kynurenine aminotransferase activity was reduced. We conclude that increased activities of kynurenine pathway enzymes in various tissues following systemic immune stimulation, in conjunction with macrophage infiltration of the affected tissue, provide a mechanism to account for increased concentrations of QUIN.

Original languageEnglish
Pages (from-to)15496-15503
Number of pages8
JournalJournal of Biological Chemistry
Volume268
Issue number21
Publication statusPublished - 01-01-1993
Externally publishedYes

Fingerprint

Quinolinic Acid
Pokeweed Mitogens
Brain
Liver
kynurenine-oxoglutarate transaminase
Duodenum
Tryptophan
Lung
Spleen
Kynurenic Acid
Cerebrospinal fluid
Kynurenine
Kidney
Tissue
kynureninase
3-Hydroxyanthranilate 3,4-Dioxygenase
Cerebrospinal Fluid
Kynurenine 3-Monooxygenase
Indoleamine-Pyrrole 2,3,-Dioxygenase
Plasmas

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Saito, Kuniaki ; Crowley, J. S. ; Markey, S. P. ; Heyes, M. P. / A mechanism for increased quinolinic acid formation following acute systemic immune stimulation. In: Journal of Biological Chemistry. 1993 ; Vol. 268, No. 21. pp. 15496-15503.
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A mechanism for increased quinolinic acid formation following acute systemic immune stimulation. / Saito, Kuniaki; Crowley, J. S.; Markey, S. P.; Heyes, M. P.

In: Journal of Biological Chemistry, Vol. 268, No. 21, 01.01.1993, p. 15496-15503.

Research output: Contribution to journalArticle

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