Inhibition by haloperidol, of adenosine 5'-triphosphate-evoked responses in rat pheochromocytoma cells

The effects of haloperidol, a typical antipsychotic drug, on adenosine 5'-triphosphate (ATP)-induced increase in intracellular Ca²⁺ concentration ([Ca]i) and inward currents were investigated using rat pheochromocytoma PC12 cells. Haloperidol (10-100 μM) significantly attenuated the rise in [Ca]i evoked by 30 μM ATP. This inhibition was not mimicked by (-)-sulpiride, an antagonist to dopamine D2-receptor. Dopamine or other dopaminergic agents did not affect the [Ca]i rise evoked by ATP. Under whole-cell voltage-clamp, haloperidol inhibited the ATP-activated current in the cells. These results suggest that haloperidol inhibits the ATP-receptor/channel, leading to the attenuation of the ATP-evoked increase in [Ca]i. Mechanisms involving dopamine receptors may not contribute to the inhibition by haloperidol.