MECHANISMS OF PEPTIDE AND PROTEIN-ABSORPTION .1. PARACELLULAR INTESTINAL TRANSPORT - MODULATION OF ABSORPTION

The significance of the paracellular pathway in both the absorption and secretion of therapeutic compounds by the intestine has received little attention to date. A growing body of literature firmly documents the importance of this aqueous pathway as a major contributor to the transepithelial flow of water and solutes in a wide spectrum of epithelia, including both the small and large intestine. The relative contributions of the paracellular and cellular pathways to intestinal absorption are discussed with respect to both diffusion and convective flow of water. Emphasis is placed on the interaction of convective flow with net intestinal absorption. The discussion of convective flow is extended to the intriguing observations that the permeability of the paracellular tight junction may be under active regulation by glucose and amino acids through cytoskeletal connections to the perijunctional actomyosin complex. The review cites studies from other epithelia, suggesting the universal character of the importance of the transport between, as well as through, cells and attempts to establish physiological criteria for assessing the contribution of paracellular transport to the intestinal absorption of therapeutic compounds, including peptides and peptidomimetics.