Transport of heterocyclic acids across rat small intestinein Vitro

Abstract

A study has been made of the steady-state fluxes of barbituric acid, six of its substituted derivatives, and 5,5-dimethyloxazolidinedione (DMO) across the wall of rat jejunumin vitro. For each of the compounds tested the mucosal (M) to serosal (S) flux was significantly larger than theS toM flux. BothM toS andS toM fluxes increased linearly with concentration, and the transport of one acid was not influenced by the presence of a tenfold greater concentration of a second heterocyclic acid. The fluxes decreased as the pH of the incubation saline was increased, but neither theM toS, nor theS toM fluxes could be described in terms of simple nonionic diffusion. It was found that the relation between the flux ratios of the transported acids and their pK _a values could be described by an equation derived from consideration of the transport of a weak acid in a series three compartment system, and it has been concluded that the three compartment system provides a good working hypothesis for the mechanism of heterocyclic acid transport across rat jejunum. It was found that the best fit of the theoretical curve to the experimental data was obtained when the ratio of permeabilities to the ionized and nonionized forms of a weak acid at one of the barriers was assigned the value 5×10⁻¹. It is suggested that this value may be characteristic of a noncellular restriction to diffusion, such as a layer of connective tissue, and substantiates previous suggestion that the intermediate compartment of the intestinal three compartment system is a component of the sub-epithelial extracellular space.