Effect of Amphotericin B on the Permeability of the Toad Bladder*

Abstract

Amphotericin B, a polyene antibiotic, stimulated Na transport in the toad bladder. This effect, similar to that of vasopressin, results from an increase in permeability of the mucosal surface to Na. The permeability of the bladder to small solutes, e. g. , potassium, chloride, and thiourea, which normally penetrate the tissue at low rates unaffected by vasopressin, was greatly increased by amphotericin B. The rate of penetration of the bladder by urea was enhanced by amphotericin B or by vasopressin to a similar extent, but the subsequent addition of the second agent failed to increase the response beyond that produced by the first. In contrast to the effects on the permeability of the bladder to solutes, amphotericin B had little effect on the net transport of water across the bladder, which was still dependent for its occurrence on the presence of vasopressin. The findings provide independent evidence to support the hypothesis that the major resistance to penetration of this tissue resides in a double series barrier, a dense diffusion, and a porous barrier, located in or near the mucosal surface. The dense diffusion barrier is affected by either amphotericin B or vasopressin to allow penetration by sodium or urea; the porous barrier is acted upon by vasopressin alone to induce bulk flow of water. Although acidification of the mucosal medium specifically stimulates sodium transport in this tissue, in the presence of amphotericin B acidification fails to enhance and, in fact, depresses sodium transport. This localizes the site of the H ion effect to the dense diffusion barrier. The fall in Na transport in the absence of serosal K is promptly reversed by amphotericin B. This confirms the hypothesis that the major effect of K removal on Na transport results from obstruction to the entry of sodium into the cells. All the effects with amphotericin B were elicited with the compound added to the mucosal bathing medium; no effects were detectable from the serosal side in the concentrations used.