Inhibition of cytochrome P450 2E1 induces an increase in extracellular dopamine in rat substantia nigra: a new metabolic pathway?

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H NissbrandtG Engberg

Abstract

We presented data previously on dopamine (DA) synthesis and catabolism in the rat substantia nigra (SN) suggesting that a substantial part of the synthesized DA in this brain part is metabolized by unknown nonclassical metabolic pathways. On the basis of that a relatively high density of cytochrome P450 2E1 (CYP 2E1) has been detected in rat SN the aim of the present study was to investigate the possibility that this enzyme is involved in the metabolism of DA. Systemic administration of either phenylethyl isothiocyanate (100 mg/kg ip), diethyldithiocarbamate (500 mg/kg, ip) or diallyl sulfide (200 mg/kg, sc or ip), three different inhibitors of cytochrome P450 2E1, induced an increase of the extracellular DA concentration in the SN, measured with microdialysis in awake rats, by 130%, 90%, and 35%, respectively. A tendency to increased concentrations of the classical DA metabolites in the dialysate from the SN was also observed in some experiments. In the striatum, no profound effects were induced by the drugs on the concentrations of DA or its metabolites. The results show that CYP 2E1 activity affects dopaminergic neurotransmission in the SN, possibly by participating in DA metabolism. Other mechanisms, such as the influence o...Continue Reading

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Citations

Apr 22, 2009·Journal of Neural Transmission·H Niazi ShahabiH Nissbrandt
Nov 7, 2007·Toxicological Sciences : an Official Journal of the Society of Toxicology·Ashu JohriDevendra Parmar
Aug 11, 2004·Clinical Pharmacokinetics·Guillermo GervasiniJulio Benitez
Dec 3, 2014·BMC Complementary and Alternative Medicine·Mona K GalalMarwa A Ibrahim
Jul 9, 2004·Drug Metabolism Reviews·Sharon Miksys, Rachel F Tyndale
Mar 21, 2009·Neuropharmacology·C ViaggiG U Corsini
Apr 25, 2003·British Journal of Pharmacology·Lisa A HowardRachel F Tyndale
Nov 15, 2011·Toxicology Mechanisms and Methods·Araceli Vences-MejíaJ Javier Espinosa-Aguirre
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May 3, 2006·Molecular and Cellular Biochemistry·Sanjay YadavDevendra Parmar
Jan 26, 2006·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Meenal Joshi, Rachel F Tyndale

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