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The purpose of the present study was to assess the effects of cyclosporine A (CyA) in the osmotic water flow response of isolated toad bladder to arginine-vasotocin (AVT) and to angiotensin II (Ang II) and AVT in isolated toad skin. CyA added to the dermal side of isolated toad skin or to the serosal side of toad bladder in concentrations of 0.42. 10(-6) M to 0.42. 10(-7) M had no effect on basal osmotic water permeability (Posm) but inhibited the hormonal response to AVT in both membranes (AVT 10(-10) M in toad bladder and 10(-8) to 10(-9) M in toad skin). CyA also inhibited the Posm response to Ang II (10(-7) M) in toad skin in concentrations of 0.42. 10(-6) M and 0.42. 10(-7) M. In toad bladder it could be demonstrated that the inhibitory effect was reversible. CyA in concentrations of 0.42. 10(-6) M inhibited the Posm response of toad skin to theophylline (3.2. 10(-3) M) and to dibutyryl cyclic AMP (6.3. 10(-3) M) suggesting an effect distal to the generation of cyclic AMP. These responses would support the possibility of a diuretic effect in the mammalian nephron.

The stimulation of transepithelial sodium transport by arginine vasotocin (AVT) and the ability of prostaglandin E2 (PGE2) to inhibit the AVT dependent sodium transport was examined on pieces of frog skin taken from different regions of the frog. The basal sodium transport was of the same magnitude in the abdominal, thoracal and upper and lower dorsal region. In all regions the sodium transport could be stimulated by AVT, though the stimulation was highest in the abdomen. Subsequent addition of PGE2 caused a significant inhibition of the AVT dependent sodium transport in the abdomen but had only minor effects on the other parts of the skin. Therefore, pieces of skin from the abdomen were selected for the remaining experiments. Addition of PGE2 to skin pieces in the presence of AVT resulted in a hyperpolarization of the cellular potential and a decrease in the transepithelial sodium transport, indicating a decreased apical sodium permeability. This was correlated with a decrease in cellular cAMP contents. We conclude that frog skin exhibits large regional differences in sensitivity to AVT and that PGE2 only modulates the natriferic effect of AVT in the abdomen.

The effect of rat atrial natriuretic peptide (rANP) on hormonal stimulated osmotic water permeability (Jw, hydrosmotic effect) and net ion transport (short-circuit current, SCC, natriferic effect) was studied on toad skin, a tissue with functional similarities to the mammalian distal nephron, in order to assess actions on transport mechanisms. Rat atrial natriuretic peptide, rANP-99-126 (rANP) inhibited stimulated SCC and Jw to submaximal concentrations of arginine vasotocin (AVT) at a site before cyclic AMP generation. The angiotensin-converting enzyme inhibitor (ACEI) MK-422 did not modify the inhibitory effect of ANP in the stimulated Jw.