EFFECT OF THEOPHYLLINE ON THE ELECTROLYTE PERMEABILITY OF THE ISOLATED SKIN OF THE TOAD BUFO-ARENARUM

1. Short-circuit current (SCC, an index of active sodium transport) increased in response to theophylline (Theo) in the isolated skin of Bufo arenarum, regardless of the presence of chloride in the bath. 2. Tissue conductance, G, and the transepithelial potential difference, PD, also increased moderately in skins bathed in chloride-free solutions (main anion: sulfate or iodide); the increases in SCC and G were fully blocked by further addition of amiloride to the epidermal bath. 3. The increase in G following theophylline was greater in the presence of chloride, whereas PD decreased; the increased G was not modified by amiloride at a concentration that completely abolished the SCC. 4. Establishment of a chloride gradient across the theophylline-treated skin whose SCC was completely abolished by amiloride or by removal of sodium from the bath, induced a diffusion current (SCCg) in a direction consistent with the transepithelial flow of chloride following its gradient. The intensity of the SCCg was directly related to the magnitude of the gradient. 5. For a given gradient, both the intensity of the SCCg and the increase in G were greater when the gradient was directed inward (i.e., when the chloride concentration was higher in the epidermal than in the dermal bath), as compared to the opposite case. 6. Exposure of the skin to an epidermal bath made hyperosmotic by addition of urea (epidermal hyperosmolarity, EH, which reversibly increases the permeability of the paracellular pathway by << opening >> the tight junctions) induced similar increases in G, whereas SCC and PD decreased irrespective of the anion present in the solution. Further addition of amiloride to the epidermal bath abolished SCC, but did not modify G. 7. No significant SCCg occurred upon exposure of the EH-treated skin to a chloride gradient, despite the fact that the increases in G brought about by Theo or EH were of similar magnitude. 8. Although an increase in the paracellular passage of ions cannot be ruled out, our observations show that a major portion of the increase in G observed after exposure to Theo is due to the activation of a pathway with both high selectivity for chloride and rectifying properties. Such characteristics strongly suggest the location of this pathway to be transcellular.