Inhibitory effect of flunarizine and cinnarizineon corticoidogenesis in isolated bovine adrenocortical cells

We investigated the effect of flunarizine and cinnarizine, Ca^2+ blockers, on corticoidogenesis(CG) in isolated bovine adrenocortical cells. The cells were incubated with flunarizine(0.8μM) or cinnarizine(0-8μM) at 37℃ for 1 or 2h in the presence of 1.2mM Ca^2+ and 100pM ACTH. In 2h-incubat ion, both drugs dose-dependently inhibited CG induced by 1.2mM Ca^2+ plus 100pM ACTH, but did not have any effect on 1h-incubation. In the absence of ACTH, however, 1.2mM Ca^2+ -induced CG was inhibited by both drugs in 1h-incubation. These results indicate that flunarizine and cinnarizine, in 1h-incubation, have no influence on the ACTH-receptor operated Ca^2+ affect other Ca^2+ channel(s) in isolated bovine adrenocorticaicells. It is also suggested that these drugs accumulate in the adrenocortical cells in long-term(2h) treatment, and also inhibit the hormone production process beyond the Ca^2+ channels.