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 microM) significantly attenuated the rise in [Ca]i evoked by 30 microM 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.
Koizumi
S
S
Division of Pharmacology, National Institute of Health Sciences, Tokyo, Japan.
Ikeda
M
M
Nakazawa
K
K
Inoue
K
K
Ito
K
K
Inoue
K
K
D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000187:drug effects; D007700:Kinetics; D016716:PC12 Cells; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D015220:Calcium Channels; D011954:Receptors, Dopamine; D010566:Virulence Factors, Bordetella; D000255:Adenosine Triphosphate; D019204:GTP-Binding Proteins; D006220:Haloperidol; D002118:Calcium