INDUCTION OF C-FOS, JUN-B AND EGR-1 EXPRESSION BY HALOPERIDOL IN PC12CELLS - INVOLVEMENT OF CALCIUM

Acute injection of haloperidol, a dopamine D2 receptor antagonist, is known to increase immediate early gene expression of the fos and jun f amilies in rodent striatal neurons. A set of gene induction, including c-fas,jun B and TIS8/egr-1, was found when haloperidol was added to P C12 cells in culture. Electrophoretic mobility-shift assays show that haloperidol-evoked gene induction was accompanied by a transient and d ose-dependent increase in AP1 and EGR-1 binding activities in these ce lls. Gene expression is tentatively explained by the rapid and transie nt increase in cytosolic free Ca2+ concentration observed upon haloper idol addition. The cytosolic calcium rise and AP1 binding activation e licited by haloperidol were dependent on extracellular Ca2+, suggestin g that haloperidol exerted its effects by promoting Ca2+ entry into PC 12 cells. The haloperidol-induced increase in API binding activity and intracellular Ca2+ was not reproduced by two other dopamine D2 recept or antagonists, sulpiride and (+)-butaclamol.