Cilostazol, an Inhibitor of Type 3 Phosphodiesterase, Stimulates Large-Conductance, Calcium-Activated Potassium Channels in Pituitary GH3 Cells and Pheochromocytoma PC12 Cells

The effects of cilostazol, a dual inhibitor of type 3 phosphodiesterase and adenosine uptake, on ion currents were investigated in pituitary GH3 cells and pheochromocytoma PC12 cells. In whole-cell configuration, cilostazol (10 μm) reversibly increased the amplitude of Ca2+-activated K+ current [IK(Ca)]. Cilostazol-induced increase in IK(Ca) was suppressed by paxilline (1 μm) but not glibenclamide (10 μm), dequalinium dichloride (10 μm), or β-bungarotoxin (200 nm). Pretreatment of adenosine deaminase (1 U/ml) or α,β-methylene-ADP (100 μm) for 5 h did not alter the magnitude of cilostazol-stimulated IK(Ca). Cilostazol (30 μm) slightly suppressed voltage-dependent l-type Ca2+ current. In inside-out configuration, bath application of cilostazol (10 μm) into intracellular surface caused no change in single-channel conductance; however, it did increase the activity of large-conductance Ca2+-activated K+ (BKCa) channels. Cilostazol enhanced the channel activity in a concentration-dependent manner with an EC50 v...