Salivary duct cells produce a hypotonic fluid that is poor in NaCl and rich in KHCO3
In the salivary glands, as in the pancreas, the ducts modify the composition of the isotonic, plasma-like primary secretion of the acinar cells. As the fluid exits the salivary acinus, it passes through an intercalated duct (see Fig. 43-10A), with typical intercalated duct cells (see Fig. 43-10C). Later, abundant mitochondria and infoldings of the basolateral membrane give the basal portion of the duct cells a characteristic striated appearance—hence the term striated duct cell (see Fig. 43-10B). This morphology goes hand in hand with high rates of active transport. In general, salivary duct cells absorb Na+ and Cl− and, to a lesser extent, secrete K+ and . Because the epithelium is not very water permeable, the lumen thus becomes hypotonic. However, significant differences are seen in the various types of salivary glands.
Reabsorption of Na+ by salivary duct cells is a two-step transcellular process (Fig. 43-11). First, Na+ enters the cell from the lumen through apical epithelial Na+ channels (ENaCs; see Table 6-2, family #14). Second, the basolateral Na-K pump extrudes this Na+. Elevated [Na+]i provides feedback inhibition by downregulating ENaC activity, presumably via the ubiquitin-protein ligase Nedd4.
FIGURE 43-11 Salivary duct transporters.
Reabsorption of Cl− is also a two-step transcellular process (see Fig. 43-11). Entry of Cl− across the apical membrane occurs via a Cl-HCO3 exchanger and CFTR. To a certain extent, apical CFTR also recycles Cl−absorbed by the Cl-HCO3 exchanger. Thus, CFTR may facilitate both secretion and Cl− reabsorption through bidirectional Cl− movement across the apical membrane. Exit of Cl− across the basolateral membrane of duct cells occurs via inwardly rectifying (ClC-2) Cl− channels.
Secretion of occurs via pathways (see Fig. 43-11) similar to those in pancreatic ducts and involves apical Cl-HCO3 exchangers and CFTR, as well as basolateral Na/HCO3 cotransporters (see p. 122). N43-5
Secretion of K+ occurs through the basolateral uptake of K+ via the Na-K pump (see Fig. 43-11). The mechanism of K+ exit across the apical membrane is not well established.
Parasympathetic stimulation decreases Na+ absorption, whereas aldosterone increases Na+ absorption by duct cells
Regulation of duct cell transport processes is less well understood in the salivary glands than in the pancreas. In the intact salivary gland (i.e., acini and ducts), secretion is stimulated primarily by parasympathetic input via ACh. In the duct cell, cholinergic agonists, acting through muscarinic receptors (mostly M3), increase [Ca2+]i and presumably activate Ca2+-dependent regulatory pathways. The effector targets of this Ca2+ signaling pathway are not known. The role played by duct cells in the increased saliva production that occurs in response to cholinergic stimulation is limited and may reflect decreased NaCl absorption more than increased KHCO3 secretion.
The specific effects of adrenergic stimulation on the transport activity of duct cells are unclear. Nevertheless, activation of the β-adrenergic receptor increases [cAMP]i and activates the CFTR Cl− channel.
Salivary duct cell function is also regulated by circulating hormones. The mineralocorticoid hormone aldosterone stimulates the absorption of NaCl and secretion of K+ by salivary duct cells in several species. Although its role has not been well examined in salivary duct cells, aldosterone in other Na+-absorbing epithelia (e.g., kidney and colon) stimulates Na+ transport by increasing both ENaC and Na-K pump activity (see pp. 765–766). Salivary duct cells may also have receptors for certain neuropeptides such as VIP, although their physiological significance remains unknown.
Salivary duct cells also secrete and take up proteins
Duct cells handle proteins in three ways. Some proteins that are synthesized by duct cells are secreted into the lumen, others are secreted into the blood, and still others are reabsorbed from the lumen to the cell.
Intralobular duct epithelial cells in rodent submandibular glands synthesize a variety of proteins that are stored in intracellular granules and are secreted in response to neurohumoral stimuli. EGF, nerve growth factor, and kallikrein are among the most abundant proteins that are packaged for secretion by these cells. Salivary duct cells may also synthesize, store, and secrete some digestive enzymes (α-amylase and ribonucleases). Degranulation of intralobular duct cells occurs primarily in response to α-adrenergic stimulation, which suggests that protein secretion by duct cells is regulated primarily by the sympathetic division.
Although regulatory peptides (i.e., glucagon and somatostatin) have also been detected in salivary duct cells, no evidence indicates that they are stored in granules or are secreted into the lumen (i.e., they may be basolaterally secreted as peptide hormones). In addition, duct cells synthesize polymeric immunoglobulin A (IgA) receptors that are responsible for the basolateral endocytosis of IgA, and they also synthesize a secretory component that facilitates the apical release of IgA.
Salivary duct cells can also remove organic substances from the duct lumen. Endocytosis of acinar proteins and other materials (e.g., ferritin) at the apical pole of the duct cell has been demonstrated immunocytochemically. In addition, salivary duct cells express the transferrin receptor (see p. 42) on the apical membrane, which indicates that some regulated endocytosis also occurs in these cells. The latter process may function to take up specific luminal substances or to traffic ion transporters to and from the apical plasma membrane.