Functional Differences in the Acinar Cells of the Murine Major Salivary Glands

In humans, approximately 90% of saliva is secreted by the 3 major salivary glands: the parotid (PG), the submandibular (SMG), and the sublingual glands (SLG). Even though it is known that all 3 major salivary glands secrete saliva by a Cl^--dependent mechanism, salivary secretion rates differ greatly among these glands. The goal of this study was to gain insight into the properties of the ion-transporting pathways in acinar cells that might account for the differences among the major salivary glands. Pilocarpine-induced saliva was simultaneously collected in vivo from the 3 major salivary glands of mice. When normalized by gland weight, the amount of saliva secreted by the PG was more than 2-fold larger than that obtained from the SMG and SLG. At the cellular level, carbachol induced an increase in the intracellular [Ca²⁺] that was more than 2-fold larger in PG and SMG than in SLG acinar cells. Carbachol-stimulated Cl^- efflux and the protein levels of the Ca²⁺-activated Cl^- channel TMEM16A, the major apical Cl^- efflux pathway in salivary acinar cells, were significantly greater in PG compared with SMG and SLG. In addition, we evaluated the transporter activity of the Na⁺-K⁺-2Cl^- cotransporters (NKCC1) and anion exchangers (AE), the 2 primary basolateral Cl^- uptake mechanisms in acinar cells. The SMG NKCC1 activity was about twice that of the PG and more than 12-fold greater than that of the SLG. AE activity was similar in PG and SLG, and both PG and SLG AE activity was about 2-fold larger than that of SMG. In summary, the salivation kinetics of the 3 major glands are distinct, and these differences can be explained by the unique functional properties of each gland related to Cl^- movement, including the transporter activities of the Cl^- uptake and efflux pathways, and intracellular Ca²⁺ mobilization.