Tight junctions and paracellular fluid and ion transport in salivary glands

Primary saliva is formed by salivary epithelial endpieces through two pathways, the transcellular and the paracellular pathways. While the mechanisms of ion transport through the transcellular pathway have been well studied, our understanding of fluid and electrolyte transport through the paracellular pathway remains rudimentary. Increasing evidence indicates that the tight junction (TJ) proteins form and regulate the paracellular pathway, although other intercellular junctions are probably involved. The structure of the TJ is complex and has not been well characterised. A functioning TJ is formed by multiple proteins, including membrane, cytoplasmic scaffolding, and signalling proteins. Paracellular fluid and electrolyte flow is mediated by high-capacity, charge- and size-restrictive small pores with a radius of 4 to 6 Å, whereas macromolecules pass through low-capacity, nonrestrictive large pores. Although the characteristics of these pores need to be further delineated, it is clear that they are under the regulation of the autonomic nervous system, endocrine, paracrine and autocrine systems, and various pathological factors. To date, the majority of the evidence for paracellular fluid and ion transport is accumulated from the studies using various epithelia other than salivary glands. Further investigations to explore the structure, function, and regulation of the paracellular pathway in salivary epithelia are needed to better understand the mechanism of saliva secretion.