Regional distribution of cytochrome P450 2D1 in the rat central nervous system

Title

Regional distribution of cytochrome P450 2D1 in the rat central nervous system

Creator

Norris P J; Hardwick J P; Emson P C

Publisher

Journal of Comparative Neurology

Date

1996
1996-03

Description

Cytochrome P450s are enzymes involved in the oxidative metabolism of numerous endogenous and exogenous molecules. The enzyme cytochrome debrisoquine/sparteine-type monoxygenase is a specific form of cytochrome P450 and is found in the liver and the brain (in the rat the enzyme is known as CYP2D1). CYP2D1 has no established role in the brain; however, it has been shown to share substrate and inhibitor specificities with the dopamine transporter and the enzyme monoamine oxygenase B. Using CYP2D-specific deoxyoligonucleotide probes and a polyclonal antibody to CYP2D1, we have mapped the distribution of CYP2D mRNA and CYP2D1-like immunoreactivity in the rat central nervous system. CYP2D1 immunoreactivity and the CYP2D mRNA signal were heterogenously distributed between brain areas. There were moderate to high levels of immunoreactivity and mRNA signal in the olfactory bulb, olfactory tubercle, cerebral cortex, hippocampus, dentate gyrus, piriform cortex, caudate putamen, supraoptic nucleus, medial habenula, hypothalamus, thalamus, medial mamilliary nucleus and superior colliculus. In the brainstem, strong CYP2D1 immuno-reactivity and CYP2D mRNA signal were observed in the substantia nigra compacta, red nucleus, interpeduncular nucleus, pontine grey, locus coeruleus, cerebellum, and the ventral horn of the spinal cord. This study indicates that CYP2D1 is widely and constitutively expressed in neuronal and some glial populations in the rat brain. The localization of CYP2D1 in several regions known to harbor catecholamines and serotonin may suggest a role for CYP2D1 in the metabolism of monoamines. (C) 1996 Wiley-Liss, Inc.

Subject

4-hydroxylation; catecholamine metabolism; debrisoquine sparteine-type; dopamine; drug-metabolism; h-3 gbr-12935 binding; human-brain; immunohistochemical localization; multiple forms; Neurosciences & Neurology; neurotoxin; parkinsons-disease; parkinsons-disease; polymorphism; striatal membranes; transporter; xenobiotics; Zoology

Format

Journal Article

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Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

244-258

Issue

2

Volume

366

Citation

Norris P J; Hardwick J P; Emson P C, “Regional distribution of cytochrome P450 2D1 in the rat central nervous system,” NEOMED Bibliography Database, accessed October 16, 2021, https://neomed.omeka.net/items/show/6657.

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