l-Cysteine sulphinate, endogenous sulphur-containing amino acid, inhibits rat brain kynurenic acid production via selective interference with kynurenine aminotransferase II

In the present study the effect of endogenous sulphur-containing amino acids, l-cysteine sulphinate, l-cysteate, l-homocysteine sulphinate and l-homocysteate, on the production of glutamate receptor antagonist, kynurenic acid (KYNA), was evaluated. The experiments comprised the measurements of (a) K...

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Published in:Neuroscience letters 2003-07, Vol.346 (1), p.97-100
Main Authors: Kocki, Tomasz, Luchowski, Piotr, Luchowska, Elzbieta, Wielosz, Marian, Turski, Waldemar A., Urbanska, Ewa M.
Format: Article
Language:English
Subjects:
Amino Acids, Sulfur - pharmacology
Animals
Biochemistry and metabolism
Biological and medical sciences
Brain
Central nervous system
Cerebral Cortex - drug effects
Cerebral Cortex - enzymology
Cysteine - analogs & derivatives
Cysteine - pharmacology
Dose-Response Relationship, Drug
Enzyme Inhibitors - pharmacology
Fundamental and applied biological sciences. Psychology
In vitro
In Vitro Techniques
Kynurenic acid
Kynurenic Acid - antagonists & inhibitors
Kynurenic Acid - metabolism
Kynurenine aminotransferase
l-Cysteine sulphinate
Male
Rats
Rats, Wistar
Sulphur-containing amino acids
Transaminases - antagonists & inhibitors
Transaminases - biosynthesis
Vertebrates: nervous system and sense organs
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Summary:In the present study the effect of endogenous sulphur-containing amino acids, l-cysteine sulphinate, l-cysteate, l-homocysteine sulphinate and l-homocysteate, on the production of glutamate receptor antagonist, kynurenic acid (KYNA), was evaluated. The experiments comprised the measurements of (a) KYNA synthesis in rat cortical slices and (b) the activity of KYNA biosynthetic enzymes, kynurenine aminotransferases (KATs). All studied compounds reduced KYNA production and inhibited the activity of KAT I and/or KAT II, thus acting most probably intracellularly. l-Cysteine sulphinate in very low, micromolar concentrations selectively affected the activity of KAT II, the enzyme catalyzing approximately 75% of KYNA synthesis in the brain. l-Cysteine sulphinate potency was higher than other studied sulphur-containing amino acids, than l-aspartate, l-glutamate, or any other known KAT II inhibitor. Thus, l-cysteine sulphinate might act as a modulator of KYNA formation in the brain.
ISSN:0304-3940
1872-7972
DOI:10.1016/S0304-3940(03)00579-2