Role of Paracellular Pathway in Nonelectrolyte Permeation Across Rat Colon Epithelium Enhanced by Sodium Caprate and Sodium Caprylate

Abstract

The enhancing effects of 0.25% sodium caprate (C10) and sodium caprylate (C8) on the paracellular permeation of seven water-soluble nonelectrolytes (inulin, polyethylene glycol 900, mannitol, erythritol, glycerol, thiourea, and urea) across the isolated rat colonic epithelium were examined using the Ussing-type chamber technique. The paracellular changes were also measured by impedance analysis. In both the presence and the absence of enhancers, the permeation clearances (Pm) for inulin (12–15 Å in molecular radius) to erythritol (3.2 Å) increased linearly with the increase in their free diffusion coefficients (Dfr), showing the existence of a paracellular shunt pathway unrestricted to any molecular size. Glycerol (2.9 Å), thiourea (2.6 Å), and urea (2.3 Å) had higher clearances than the expected linear values, showing the existence of a restricted paracellular or transcellular pathway. Both C10 and C8 increased the permeabilities in the two pathways, but C10 was more effective than C8. The increase in the permeabilities via the shunt pathway caused by the enhancers was greater than that via the restricted pathway, and thus, the two-phase pattern in the relationship of Pm and Dfr was similar to that in the absence of enhancers. The transcellular permeabilities for urea and thiourea, which were obtained from the efflux experiments, were increased by the enhancers. However, the relative increase caused by C10 was smaller than that of the paracellular-restricted permeabilities. The paracellular changes probably were due to the increase in pore area per unit diffusive path length. A decrease in the resistance of the intercellular junctions involving a simultaneous increase of membrane capacitance was observed in the presence of C10, corresponding to an increase of pore area per unit path length. The effect of C10 on the paracellular permeability was reversible, and the junctional resistance, membrane capacitance, and Pm of mannitol returned to the control level following the removal of C10.