We investigated the effect of Ca2+-channel antagonists, Nicardipine (N), Verapamil (V) and Flunarizine (F), on the corticoidogenesis (CG) in primary cultured bovine adrenocortical cells. To examine the effect on receptor operated Ca2+-channel (ROC) and voltage operated Ca2+-channel (VOC), involved in corticoid synthesis, adrenocorticotropic hormone (ACTH) and high-K+ were used respectively. With or without the antagonists, cells were incubated at 37°C for 1h in the presence of ACTH (100pM) or K+ (30mM). Corticoid was measured fluorometrically using cortisol as the standard. N and V inhibited not only ACTH-induced CG, but high K+-induced CG in a concentration-dependent manner. However, F inhibited only high K+-induced CG, and did not affect ACTH-induced CG. These inhibitions were observed at the low micromolar concentrations (below 40μM) of the antagonists. In the regulation of corticoid synthesis, we indicate that F has an inhibitory effect on VOC without ROC; on the other hand, N and V inhibit both ROC and VOC.
