Regulation of Paracellular Permeability by Secretagogues in Parotid Acinar Cells

Saliva plays a crucial role in maintaining oral function. Although paracellular transport in the acini is essential for primary saliva production, the regulatory mechanism of tight junctions, which determine the paracellular permeability of epithelium, remains to be fully elucidated. The lack of an established, fully functional acinar cell line is one of the reasons limiting the research progress. We previously reported that acinar cells cultured in the presence of PP1, a Src kinase inhibitor, maintained a high transepithelial electrical resistance and the expression of intercellular adhesion molecules. By using the culture, we investigated the change in paracellular permeability upon muscarinic and ϐ-adrenergic stimulation. Carbachol, a muscarinic agonist, significantly decreased transepithelial electrical resistance, indicating an increase in ionic permeability, which is necessary for primary saliva production. In contrast, isoproterenol, a ϐ-adrenergic agonist, caused no change in the transepithelial electrical resistance. The paracellular flux of 4-kDa dextran was increased by both agonists. These results are consistent with previous studies that ionic permeability is mainly regulated by parasympathetic nerves while leakage of serum protein into saliva was not different between two stimulations. Protein levels of claudins-3 and -4 did not change during the 15-min stimulation period, suggesting that the permeability alterations are due to rapid mechanism, such as change in subcellular localization rather than protein degradation.