Esteve L, Haby C, Rodeau J L, Humblot N, Aunis D, Zwiller J
INSERM U338, Centre de Neurochimie, Strasbourg, France.
Neuropharmacology. 1995 Apr;34(4):439-48. doi: 10.1016/0028-3908(95)00006-r.
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.
已知急性注射多巴胺 D2 受体拮抗剂氟哌啶醇可增加啮齿动物纹状体神经元中 fos 和 jun 家族的即刻早期基因表达。当在培养的 PC12 细胞中加入氟哌啶醇时，发现了一组基因诱导现象，包括 c-fos、jun B 和 TIS8/egr-1。电泳迁移率变动分析表明，氟哌啶醇诱发的基因诱导伴随着这些细胞中 AP1 和 EGR-1 结合活性的短暂且剂量依赖性增加。基因表达初步解释为加入氟哌啶醇后观察到的胞质游离 Ca2+ 浓度的快速且短暂增加。氟哌啶醇引起的胞质钙升高和 AP1 结合激活依赖于细胞外 Ca2+，这表明氟哌啶醇通过促进 Ca2+ 进入 PC12 细胞发挥其作用。另外两种多巴胺 D2 受体拮抗剂舒必利和(+)-布他拉莫并未重现氟哌啶醇诱导的 AP1 结合活性和细胞内 Ca2+ 的增加。
