Phenothiazines increase active sodium transport across the isolated toad skin

Fluphenazine (FPZ) and trifluoperazine (TFP) are phenothiazine derivatives commonly used as antipsychotic tranquilizers. Their mechanism of action is incompletely understood. Epidermal addition of each drug promoted biphasic short-circuit current (SCC) changes across isolated pelvic skin of Bufo arenarum toads. By means of radiotracers fluxes, SCC was found to be given by the algebraic sum of net sodium and chloride transport. A readily stimulant effect was detected a low concentrations (from 1 X 10(-6) mol/l up to 1 X 10(-4) mol/l for FPZ, from 1 X 10(-5) mol/l up to 3.2 X 10(-4) mol/l for TFP) above which inhibition prevailed. Dermal FPZ also stimulated SCC. A higher concentration and time threshold were required. Epidermal 1 X 10(-5) mol/l FPZ stimulation was partially reversible, with a diminished membrane resistance and enhancement of sodium influx, without alteration of sodium efflux or net chloride transport. It could be prevented by amiloride pretreatment, or diminished by dermal sodium removal. Variation of epidermal bulk pH from 5.8 to 8.7 demonstrated that ionized and nonionized molecules contribute to FPZ's effect. Our results suggest that SCC stimulation elicited by FPZ and TFP may be a consequence of direct or indirect modifications on apical sodium conductance.