Diffusion of Weak Acids across the Toad Bladder : Influence of pH on non-ionic permeability coefficients

Studies have been carried out, using the toad bladder, to determine the influence of pH on the permeability coefficients (K (trans)) of the non-ionic species of (a) a series of aliphatic acids ranging from propionic to octanoic and (b) the aromatic acids, benzoic and acetylsalicylic. The data demonstrate that as the acidity of the mucosal bathing solution is increased by changing pH from 6 to 4, the fluxes of propionic, butyric, and acetylsalicylic acids increase in direct proportion to the increase in the calculated non-ionic concentration; the permeability coefficients, therefore, remain constant. However, the fluxes of the six, seven, and eight carbon aliphatic acids and benzoic acid rise only slightly despite an almost tenfold increase in non-ionic concentration, the K (trans) falling from approximately 20,000 x 10(-7) cm sec.(-1) at pH 6 to approximately 2500 x 10(-1) cm sec.(-1) at pH 4. It has been tentatively proposed that the common characteristic of the compounds exhibiting this anomalous behavior is their non-polarity and high degree of lipid solubility. Possible explanations for the differences observed between the more lipid-soluble and less lipid-soluble compounds have been considered.