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1 Amiloride inhibits Na transport and short-circuit current (SCC) across the toad bladder. It is 1000 times more active at the mucosal than serosal surface. The lowest effective concentration was 10^-7 M.

2. The inhibition was non-competitive with the sodium on the mucosal side of the bladder.

3. Vasopressin, cyclic adenosine monophosphate (AMP) and aldosterone increased Na transport and SCC across the bladder and these effects were inhibited by amiloride.

4. The antagonism of amiloride for vasopressin was non-competitive.

5. Amphotericin B also increases Na transport across the bladder but its action was not changed by amiloride.

6. Amiloride was without effects on SCC and diffusion potentials in bladders metabolically inhibited with CN^- and iodoacetic acid (IAA).

7. Neither plasma albumin, Ca²⁺ nor adenosine triphosphate (ATP) altered the effects of amiloride.

8. The only structural analogue of amiloride found to reduce SCC similarly was guanidine which was 1000 times less active. Pyrazine and a substituted pyrazine analogue were without effect. Neither guanidine nor the substituted pyrazine compound were competitive with amiloride.

9. Amiloride had no effect on the osmotic permeability of the toad bladder either in the presence or absence of vasopressin.

10. Na transport across the toad colon was also reduced by 10^-5 M amiloride at the mucosal surface.

11. The possible mechanism of action of amiloride is discussed.

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