| A mechanism for increased quinolinic acid formation following acute systemic immune stimulation. | |
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MedLine Citation:
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PMID: 8340378 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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K Saito; J S Crowley; S P Markey; M P Heyes |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 268 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 1993 Jul |
Date Detail:
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Created Date: 1993-08-30 Completed Date: 1993-08-30 Revised Date: 2003-11-14 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 15496-503 Citation Subset: IM |
Affiliation:
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Section on Analytical Biochemistry, National Institute of Mental Health, Bethesda, Maryland 20892. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anthranilic Acids / metabolism Duodenum / enzymology, metabolism Female Gerbillinae Hydrocortisone / pharmacology Immunization* Kidney / enzymology, metabolism Kinetics Kynurenine / metabolism* Liver / enzymology, metabolism Lung / enzymology, metabolism Pokeweed Mitogens / immunology Quinolinic Acid / blood, cerebrospinal fluid, metabolism* Spleen / enzymology, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Anthranilic Acids; 0/Pokeweed Mitogens; 118-92-3/anthranilic acid; 343-65-7/Kynurenine; 50-23-7/Hydrocortisone; 89-00-9/Quinolinic Acid |
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