Trifluoperazine stimulated sodium transport through the apical surface of isolated frog skin.

When added to the apical solution of isolated frog skin, the calmodulin antagonist trifluoperazine (TFP)* stimulated the short-circuit current (SCC) in a dose-dependent manner. The increase in SCC was due to an enhanced active transepithelial Na transport. After addition of TFP (15 microM) the intracellular voltage depolarized, showing that TFP acts by increasing the sodium (Na) permeability of the apical membrane. The TFP-induced increase in SCC was not accompanied by an increase in prostaglandin E2 release from the skins as observed by basolateral addition of TFP. When the apical Na concentration in fast-flow experiments was changed from 0 to 50 mM, the SCC increased promptly and then reclined. The presence of TFP in the apical solution abolished this recline. The apparent inhibition constant for amiloride changed in the presence of TFP from 1.42 +/- 0.12 microM to 0.38 +/- 0.05 microM (n = II) and TFP abolished the inhibition of SCC caused by high apical Na concentrations. These observations indicate that TFP acts by abolishing the Na self-inhibition of the Na channels. Calmidazolium and chlorpromazine stimulated the SCC to the same degree and in the same concentration range as TFP, suggesting that the effect of TFP was not mediated by the Ca2+-calmodulin complex.