title: Induction of c-fos, jun B and egr-1 expression by haloperidol in PC12 cells: involvement of calcium.
abstract: Acute injection of haloperidol, a dopamine D2 receptor antagonist, is known to increase immediate early gene expression of the fos and jun families in rodent striatal neurons. A set of gene induction, including c-fos, jun B and TIS8/egr-1, was found when haloperidol was added to PC12 cells in culture. Electrophoretic mobility-shift assays show that haloperidol-evoked gene induction was accompanied by a transient and dose-dependent increase in AP1 and EGR-1 binding activities in these cells. Gene expression is tentatively explained by the rapid and transient increase in cytosolic free Ca2+ concentration observed upon haloperidol addition. The cytosolic calcium rise and AP1 binding activation elicited by haloperidol were dependent on extracellular Ca2+, suggesting that haloperidol exerted its effects by promoting Ca2+ entry into PC12 cells. The haloperidol-induced increase in AP1 binding activity and intracellular Ca2+ was not reproduced by two other dopamine D2 receptor antagonists, sulpiride and (+)-butaclamol.
authors.affiliation: INSERM U338, Centre de Neurochimie, Strasbourg, France.
authors.forename: L
authors.initials: L
authors.lastname: Esteve
authors.forename: C
authors.initials: C
authors.lastname: Haby
authors.forename: J L
authors.initials: JL
authors.lastname: Rodeau
authors.forename: N
authors.initials: N
authors.lastname: Humblot
authors.forename: D
authors.initials: D
authors.lastname: Aunis
authors.forename: J
authors.initials: J
authors.lastname: Zwiller
mesh_terms: D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016762:Genes, fos; D016758:Genes, jun; D006220:Haloperidol / Q000494:pharmacology*; D008969:Molecular Sequence Data; D016716:PC12 Cells; D051381:Rats; D017208:Rats, Wistar; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation
chemical_list: D006220:Haloperidol; D002118:Calcium