Chlorpromazine activates chloride currents in Xenopus oocytes.
Xenopus oocytes are frequently used for in vivo expression of DNA and RNA, especially those encoding ion channel proteins. Accordingly, it is important to understand the expression and control of endogenous conductances. Ionic currents were studied in native Xenopus oocytes with two-microelectrode voltage-clamp technique to characterize the actions of chlorpromazine (CPZ) and trifluroperazine (TFP), two widely used antipsychotic drugs. External application of CPZ or TFP markedly stimulated endogenous conductances in a dose-dependent and reversible fashion. The current-voltage (I-V) relationship was non linear and dependent on the presence of external chloride. The CPZ-activated currents were inhibited by Cl- channel blockers. Although the removal of external Ca2+ had no effect on CPZ-induced conductances, the injection of BAPTA, a Ca2+ chelator, abolished endogenous activity. Thapsigargin also inhibited channel activity suggesting that CPZ acts through intraoocyte Ca2+ release. The calmodulin inhibitors, calmidazolium and W-7, failed to mimic the action of CPZ. These data provide evidence for external or internal phenothiazine receptors which when activated by CPZ induces Ca(2+)-dependent Cl- channel activity in endogenous native oocytes.
Quamme
G A
GA
Department of Medicine, University of British Columbia, Vancouver Hospital, BC, Canada.
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002147:Calmodulin / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology; D002614:Chelating Agents / Q000494:pharmacology; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000502:physiology; D002746:Chlorpromazine / Q000494:pharmacology*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D009865:Oocytes; D018408:Patch-Clamp Techniques; D011954:Receptors, Dopamine / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology; D014981:Xenopus
D014150:Antipsychotic Agents; D002147:Calmodulin; D002614:Chelating Agents; D018118:Chloride Channels; D004791:Enzyme Inhibitors; D011954:Receptors, Dopamine; C028052:phenothiazine receptor; D014268:Trifluoperazine; D004533:Egtazic Acid; D019284:Thapsigargin; D000252:Calcium-Transporting ATPases; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium; D002746:Chlorpromazine