A functional genomic study of the effects of antipsychotic agent chlorpromazine in PC12 cells.
Expression profiling using methods of functional genomics can be used to investigate changes in gene transcription induced by drug treatment, which may lead to discovery of new potential drug targets. Antipsychotic agents alleviate symptoms of schizophrenia but the mechanism behind their clinical efficacy is unclear. We have used the PC12 cell line as a model to characterize effects of the antipsychotic drug chlorpromazine on gene expression using high-density complementary DNA array filters prepared from a rat brain entorhinal cortex complementary DNA library. Chlorpromazine treatment positively regulated the expression of several clones, five of which were selected for further characterization. Northern blotting experiments confirmed the increased expression of these genes after chlorpromazine treatment. Sequencing revealed that two clones were cytochrome c oxidase and three were novel genes. Characterization of the function of these genes could increase our understanding of the mechanisms of action of antipsychotic drugs, and might be beneficial for the development of more effective agents.
Kontkanen
O
O
Laboratory of Molecular Pharmacology, A.I.Virtanen Institute, University of Kuopio, Finland.
Lakso
M
M
Wong
G
G
Castrén
E
E
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002746:Chlorpromazine / Q000494:pharmacology*; D018076:DNA, Complementary; D003576:Electron Transport Complex IV / Q000235:genetics*; D018728:Entorhinal Cortex / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D015723:Gene Library; D023281:Genomics / Q000379:methods; D020411:Oligonucleotide Array Sequence Analysis; D016716:PC12 Cells; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats
D014150:Antipsychotic Agents; D018076:DNA, Complementary; D012333:RNA, Messenger; D003576:Electron Transport Complex IV; D002746:Chlorpromazine