FK506 attenuates 1-methyl-4-phenylpyridinium- and 3-nitropropionic acid-evoked inhibition of kynurenic acid synthesis in rat cortical slices

• Authors: E. Luchowska , P. Luchowski , M. Wielosz , W.A. Turski , E.M. Urbanska
• Languages of publication: EN

Abstracts

EN

Kynurenic acid (KYNA), the only known endogenous glutamate antagonist, is produced in the brain by kynurenine aminotransferases (KATs) I and II. Mitochondrial toxins, 1-methyl-4-phenylpyridinium (MPP+) and 3-nitropropionic acid (3-NPA), were previously shown to reduce KYNA synthesis via interference with KAT I and II. Data presented here demonstrate that immunophilin ligand, FK506 (10-130 muM), but not CsA (1-50 muM), or ryanodine receptor blocker, dantrolene (1-100 muM), enhances the formation of KYNA in cortical slices. FK506, but not CsA or dantrolene, abolished the inhibition of KYNA synthesis evoked by MPP+ and 3-NPA. None of studied compounds influenced the activity of KAT I and KAT II. FK506 is the first among currently used drugs that might stimulate KYNA synthesis. This effect does not seem to arise from the interference with KATs or calcineurin activity.

Keywords

EN

CYCLOSPORIN A; DANTROLENE; IN VITRO; KYNURENIC ACID; MITOCHONDRIAL INHIBITOR; RAT

Discipline

• EXPERIMENTAL_BIOLOGY_&_MEDICINE: EXPERIMENTAL BIOLOGY & MEDICINE

• Journal: Acta Neurobiologiae Experimentalis
• Year: 2003
• Volume: 63
• Issue: 2
• Pages: 101-108

Contributors

author

E. Luchowska

author

P. Luchowski

author

M. Wielosz

author

W.A. Turski

author

E.M. Urbanska

• Document Type: ARTICLE
• Publication order reference: E. Luchowska, Department of Pharmacology and Toxicology, Medical University, Jaczewskiego 8, 20?090 Lublin, Poland