| First Author | Chiarugi A | Year | 1996 |
| Journal | J Neurochem | Volume | 67 |
| Issue | 2 | Pages | 692-8 |
| PubMed ID | 8764597 | Mgi Jnum | J:34169 |
| Mgi Id | MGI:81638 | Doi | 10.1046/j.1471-4159.1996.67020692.x |
| Citation | Chiarugi A, et al. (1996) Kynurenine disposition in blood and brain of mice: effects of selective inhibitors of kynurenine hydroxylase and of kynureninase. J Neurochem 67(2):692-8 |
| abstractText | To study the regulation of the synthesis of quinolinic and kynurenic acids in vivo, we evaluated (a) the metabolism of administered kynurenine by measuring the content of its main metabolites 3-hydroxykynurenine, anthranilic acid, and 3-hydroxyanthranilic acid in blood and brain of mice; (b) the effects of (m-nitrobenzoyl)alanine, a selective inhibitor of kynurenine hydroxylase and of (o-methoxybenzoyl) alanine, a selective inhibitor of kynureninase, on this metabolism; and (c) the effects of (o-methoxybenzoyl)alanine on liver kynureninase and 3-hydroxykynureninase activity. The conclusions drawn from these experiments are (a) the disposition of administered kynurenine preferentially occurs through hydroxylation in brain and through hydrolysis in peripheral tissues; (b) (m-nitrobenzoyl)alanine, the inhibitor of kynurenine hydroxylase, causes the expected changes in brain kynurenine metabolism, such as a decrease of 3-hydroxykynurenine, and an increase of kynurenic acid; and (c) (o-methoxybenzoyl)alanine, the kynureninase inhibitor, increases brain concentration of the cytotoxic compound 3-hydroxykynurenine, and unexpectedly does not reduce brain concentration of 3-hydroxyanthranilic acid, the direct precursor of quinolinic acid. Taken together, the experiments suggest that the systemic administration of a kynurenine hydroxylase inhibitor is a rational approach to increase the brain content of kynurenate and to decrease that of cytotoxic kynurenine metabolites, such as 3-hydroxykynurenine and quinolinic acid. |
