TIZOLEMIDE-INDUCED CHANGES OF PASSIVE TRANSPORT COMPONENTS ACROSS THE BASOLATERAL MEMBRANE OF ISOLATED FROG-SKIN

The effect of tizolemide on transepithelial Na transport was investigated in isolated frog skin. Tizolemide (2-5 mM, serosal side) decreased transepithelial Na transport (measured as short circuit current and as net Na flux) within 60 min to 25-40% of the control level resulting from reduction of the unidirectional Na influx. Intracellular recording with microelectrodes revealed that these changes were associated with depolarization of the intracellular space to < 40% of the control values (averaging - 71.7 .+-. 5.1 mV) which is a consequence of a decrease in conductance of the basolateral border to .apprx. 25% of the control values. The conductance of the apical border was only slightly reduced. Evidently, tizolemde blocks the partial conductance of K at the basolateral border which secondarily diminishes transepithelial Na transport due to a decrease of the driving force for apical border Na entry. A certain degree of inhibition of the Na-K-ATPase by tizolemide cannot be excluded. When vasopressin (ADH) was added to frog skin after treatment with tizolemide, the response was markedly reduced compared to that of untreated control preparations. Under these conditions, the conductance of the basolateral border increased while the apical border remained little influenced by the hormone, opposite to the response of frog skins under control conditions. The mode of action of ADH is more complex than previously recognized and includes effects at the basolateral border.