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The effect of Cu²⁺ in concentrations from 1 x 10^–7 to 1 x 10^–4 mol/1 on water movement across the toad urinary bladder in vitro was studied. Although Cu²⁺ did not alter the permeability to water by itself, it strongly inhibited the hydrosmotic response induced by oxytocin and theophylline. This effect was present only when the ion was added to the serosal side. The observed inhibition was not completely reversible even at the lower Cu²⁺ concentrations. No interaction of Cu²⁺ with cyclic AMP was observed. However, a reversible inhibitory effect of the ion on the hydrosmotic response induced by increasing tonicity of the medium was demonstrated. In this case Cu²⁺ was effective from both sides. It is concluded that Cu²⁺ has two effects: (1) a non-reversible action on the cyclase system, inhibiting the responses to oxytocin and theophylline; (2) a reversible action on the 'osmosensitive mechanism', inhibiting the response induced by increasing tonicity.

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