Chlorpromazine and related phenothiazines inhibit the ATP-sensitive K+ channel.
Whole-cell, current clamp, single channel recordings and 86Rb+ flux techniques were used to show that phenothiazines inhibit ATP-sensitive K+ channels (KATP) in HIT-T15 beta-cells. Chlorpromazine inhibition was observed when KATP channels were activated by ATP depletion or by direct treatment with a classical KATP channel opener, diazoxide. The order of potency of the phenothiazines tested was chlorpromazine greater than triflupromazine greater than fluphenazine greater than trifluopromazine with IC50 values of 1, 4, 6 and 20 microM, respectively. The inhibition was reversible.
Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France.
M
M
Müller
J R
JR
De Weille
M
M
Lazdunski
D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002746:Chlorpromazine / Q000494:pharmacology*; D003981:Diazoxide / Q000494:pharmacology; D004594:Electrophysiology; D007340:Insulinoma / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects*; D012414:Rubidium Radioisotopes; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D014150:Antipsychotic Agents; D015221:Potassium Channels; D012414:Rubidium Radioisotopes; D000255:Adenosine Triphosphate; D003981:Diazoxide; D002746:Chlorpromazine