Regional and cellular expression of CYP2D6 in human brain: higher levels in alcoholics

Cytochrome P450 (CYP) 2D6 is expressed in liver, brain and other extrahepatic tissues where it metabolizes a range of centrally acting drugs and toxins. As ethanol can induce CYP2D in rat brain, we hypothesized that CYP2D6 expression is higher in brains of human alcoholics. We examined regional and...

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Veröffentlicht in:	Journal of neurochemistry 2002-09, Vol.82 (6), p.1376-1387
Hauptverfasser:	Miksys, Sharon, Rao, Yushu, Hoffmann, Ewa, Mash, Deborah C., Tyndale, Rachel F.
Format:	Artikel
Sprache:	eng
Schlagworte:	Adult Aged alcoholism Alcoholism - enzymology Alcoholism - pathology Alcoholism and acute alcohol poisoning Antibody Specificity Biological and medical sciences Blotting, Southern Brain - enzymology Brain - pathology Brain Chemistry Cerebellum - enzymology Cerebellum - pathology Cytochrome P-450 CYP2D6 - analysis Cytochrome P-450 CYP2D6 - biosynthesis Cytochrome P-450 CYP2D6 - genetics cytochrome P450 CYP2D6 drug metabolism Frontal Lobe - enzymology Frontal Lobe - pathology Genotype Hippocampus - enzymology Hippocampus - pathology human brain Humans Immunoblotting Immunohistochemistry Medical sciences Middle Aged Neurons - enzymology Neurons - pathology neurotoxicity Organ Specificity Purkinje Cells - enzymology Purkinje Cells - pathology Pyramidal Cells - enzymology Pyramidal Cells - pathology RNA, Messenger - analysis RNA, Messenger - biosynthesis Smoking - metabolism Smoking - pathology Toxicology
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Zusammenfassung:	Cytochrome P450 (CYP) 2D6 is expressed in liver, brain and other extrahepatic tissues where it metabolizes a range of centrally acting drugs and toxins. As ethanol can induce CYP2D in rat brain, we hypothesized that CYP2D6 expression is higher in brains of human alcoholics. We examined regional and cellular expression of CYP2D6 mRNA and protein by RT‐PCR, Southern blotting, slot blotting, immunoblotting and immunocytochemistry. A significant correlation was found between mean mRNA and CYP2D6 protein levels across 13 brain regions. Higher expression was detected in 13 brain regions of alcoholics (n = 8) compared to nonalcoholics (n = 5) (anovap
ISSN:	0022-3042 1471-4159
DOI:	10.1046/j.1471-4159.2002.01069.x