The effect of bile acid on the activation of amiloride-sensitive sodium channels in frog skin.

Abstract

The effect of the bile acid, deoxycholic acid (DOC), on the transport properties of isolated frog skin was studied under short-circuit conditions. The addition of DOC (1 mM) to the apical side of the frog skin induced a threefold increase in the short-circuit current (Iac). This effect was inhibited by amiloride. DOC also increased the conductance of the preparation by two different mechanisms. At low concentrations (< 2.5 mM) it activated amiloride-sensitive sodium channels. At higher concentrations of DOC, basolateral-apical unindirectional fluxes, measured with 22Na+, 36Cl-. [14C]mannitol and [14C]inulin, showed a selective increase in the permeability to Na+, Cl- and mannitol in relation to [14C]inulin. These data suggest that sodium and chloride ions use the same diffusional pathway across the preparation. This pathway discriminates between NaCl and mannitol, and discriminates even more in relation to inulin. The effects of DOC are additive to those of cAMP (1 mM). ADH (20 mU ml-1), prostaglandin E2 (0.1 microM) or forskolin (10 microM). It is concluded from our study that the final effect of DOC in stimulating the Isc in frog skin is through the activation of amiloride-sensitive sodium channels. However, since DOC is liposoluble, a direct activation of an adenylate cyclase or of phosphokinase A cannot be excluded.