Cellular localization and regional distribution of CYP2D6 mRNA and proteinexpression in human brain

The cytochrome P4502D6 (CYP2D6) is involved in the biotransformation of man y drugs which predominantly act in the central nervous system (CNS), includ ing opioids, various psychotrophic drugs and neurotoxins, Until now, howeve r, only controversial information is available regarding the presence of CY P2D6 in CNS, In this study, the regional and cellular expression of CYP2D6 transcripts and proteins in postmortem brain tissues of three individuals w as analysed, A combination of in-situ hybridization coupled with immunohist ochemistry on adjacent sections allowed simultaneous detection of CYP2D6 mR NA and protein, However, discrepancies existed in the results such that the mRNA was more widely distributed in the brain areas analysed compared to t he protein, Neuronal cells, as well as glial cells, showed labelling for mR NA in brain regions such as the neocortex, caudate nucleus, putamen, globus pallidus, hippocampus, hypothalamus, thalamus, substantia nigra and cerebe llum, In contrast, CYP2D6 protein was primarily localized in large principa l neurons such as pyramidal cells of the cortex, pyramidal cells of the hip pocampus, and Purkinje cells of the cerebellum, In glial cells, CYP2D6 prot ein was absent, These results provide clear evidence of CYP2D6 expression i n certain regions of the CNS and may indicate the role CYP2D6 plays in a nu mber of drug interactions that are of potential clinical importance for neu rological diseases, Pharmacogenetics 11:237-245 (C) 2001 Lippincott William s & Wilkins.