title: Antipsychotic Drugs Differentially Affect mRNA Expression of Genes Encoding the Neuregulin 1-Downstream ErbB4-PI3K Pathway.
abstract: OBJECTIVE
  The PIK3CD gene encodes the delta catalytic subunit of phosphoinositide 3-kinase (PI3K), an element of the neuregulin 1-downstream ErbB4-PI3K signaling pathway, which was recently identified as a molecular target for the treatment of schizophrenia. The aim of the study was to examine the effect of haloperidol (HALO), clozapine (CLO), olanzapine (OLA), quetiapine (QUE) and amisulpride (AMI) on the mRNA and protein expression of genes encoding the elements of ErbB4-PI3K pathway, in a human central nervous system cell line.
  
  
  METHODS
  The U-87MG human glioblastoma cell line was used as an experimental model. Quantitative polymerase chain reaction was used to examine the expression of mRNA and enzyme-linked immunosorbent assay for protein expression.
  
  
  RESULTS
  At concentrations reached in clinical settings in the brain, CLO, as well as OLA and QUE to a lesser extent, but not AMI and probably not HALO, decreased the mRNA expression of PIK3CD. Protein expression of the gene did not confirm the mRNA expression profile.
  
  
  CONCLUSIONS
  The tested antipsychotic drugs (APDs) in the U-87MG glioblastoma cell line differentially regulates the mRNA expression of PIK3CD; however, the protein expression does not confirm these findings. The results of the study may help deepen the understanding of the mechanism of action of APDs.
authors.affiliation: Department of Pharmacology and Toxicology, Medical University of Lodz, Lodz, Poland.
authors.forename: Michał Seweryn
authors.initials: MS
authors.lastname: Karbownik
authors.forename: Janusz
authors.initials: J
authors.lastname: Szemraj
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Wieteska
authors.forename: Adam
authors.initials: A
authors.lastname: Antczak
authors.forename: Paweł
authors.initials: P
authors.lastname: Górski
authors.forename: Edward
authors.initials: E
authors.lastname: Kowalczyk
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Pietras
mesh_terms: D000077582:Amisulpride; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003024:Clozapine / Q000494:pharmacology; D005786:Gene Expression Regulation; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D020890:Neuregulin-1 / Q000235:genetics*; D000077152:Olanzapine; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D000069348:Quetiapine Fumarate / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D066247:Receptor, ErbB-4 / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D013469:Sulpiride / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D014150:Antipsychotic Agents; C094131:NRG1 protein, human; D020890:Neuregulin-1; D012333:RNA, Messenger; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; D013469:Sulpiride; D000077582:Amisulpride; D019869:Phosphatidylinositol 3-Kinases; C587689:ERBB4 protein, human; D066247:Receptor, ErbB-4; D003024:Clozapine; D006220:Haloperidol; D000077152:Olanzapine