The major constituents of saliva are water, electrolytes, and a few enzymes. The uniqueproperties of this GI juice are (1) its large volume relative to the mass of glands that secrete saliva, (2) its low osmolality, (3) its high K+ concentration, and (4) the speciﬁc organic materials it contains.
Compared with other secretory organs of the GI tract, the salivary glands elaborate a remarkably large volume of j uice per gram (g) of tissue. Thus, for example, an entire pancreas may reach a maximal rate of secretion of 1 milliliter (mL)/minute, whereas at the highest rates of secretion in some animals, a tiny submaxillary gland can secrete 1 mL/g/minute, a 50-fold higher rate. I n humans, the salivary glands secrete at rates severalfold higher than other GI organs per unit weight of tissue.
The osmolality of saliva is signiﬁcantly lower than that of plasma at all but the highest rates of secretion, when the saliva becomes isotonic with plasma. As the secretory rate of the salivon increases, the osmolality of its saliva also increases. The concentrations of electrolytes in saliva vary with the rate of secretion.
The K+ concentration of saliva is 2 to 30 ti
stimulated. The relationships between ion concentrations and flow rates, vary somewhat, depending on
the stimulus. The relationships shown in Figure 7-3 are explained by two basic types of studies that
indicate how the ﬁnal saliva is produced. First, ﬂuid collected by micropuncture of the
intercalated ducts contains Na+, K+, Cl−, and in concentrations approximately equal to their plasma concentrations. This ﬂuid also is isotonic to plasma. Second, if one perfuses a salivary gland duct with ﬂuid containing ions in concentrations similar to those of plasma, Na+ and Cl− concentrations are decreased and K and concentrations are increased when the ﬂuid is collected at the duct opening. The ﬂuid also becomes hypotonic, and the longer the ﬂuid remains in the duct (i.e., the slower the rate of perfusion), the greater are the changes. These data indicate, ﬁrst, that the acini secrete a ﬂuid similar to plasma in its concentration of ions and, second, that as the ﬂuid moves down the duct, Na+ and Cl−
are reabsorbed and K+ and are secreted into the saliva. The higher the ﬂow of saliva, the less time is available for modiﬁcation, and the ﬁnal saliva more closely resembles plasma in its ionic makeup. At low ﬂow rates K+ increases considerably, and Na+ and Cl− decrease. Because most salivary agonists
stimulate secretion, the concentration remains relatively high, even at high rates of secretion. Some K+ and are reabsorbed in exchange for Na, but much more Na+ and Cl− leave the duct, thus causing the saliva to become hypotonic. Because the duct epithelium is relatively impermeable to water, the ﬁnal product remains hypotonic.
Current evidence indicates that Cl− is the primary ion that is actively secreted by the acinar cells. No evidence exists for direct active secretion of Na. The secretory mechanism for Cl− is inhibited by ouabain, a ﬁnding indicating that it depends on th
aquaporin 5 apical water channel. There may also be a Ca2+ -activated K channel in the basolateral membrane. Exodus of K+ increases the electronegativity of the cytosol and thereby increases the driving force for the entry of Cl − and into the lumen. Agents that stimulate salivary secretion increase the activity of all these channels and transport processes.
Within the ducts, Na+ and Cl− are actively absorbed and K+ and are actively secreted. These processes are also inhibited by ouabain and depend on the Na gradient created by the Na+ , K+ -adenosine triphosphatase (ATPase) in the basolateral membrane. The apical membrane contains a Na+ channel, and its movement into the cell supports the electrogenic movement of Cl− into the cell through Cl−
channels. The Na/KATPase pumps Na+ out while a Cl− channel in the basolateral membrane transports it out of the cell. Cl− reabsorption also occurs via the paracellular pathway. K is secreted through apical channels into the saliva. To secrete into the lumen, must be concentrated within the cell. This occurs via an Na/ transporter in the basolateral membrane, which is driven by the Na+ gradient. leaves the cell either through the apical cyclic adenosine monophosphate (cAMP)-activated CFTR (cystic ﬁbrosis transmembrane regulator) Cl− channel or via the Cl−/ exchanger at the apical membrane. The tight junctions of the ductule epithelium are relatively impermeable to water when compared with those of the acini. The net results are a decrease in Na+−+ and +Cl− concentrations and an increase in K+ and concentrations, as well as pH, as the saliva moves down the duct. More ions leave than water (HO), and the saliva becomes hypotonic. Aldosterone acts at the luminal membrane to increase the absorption of Na and the secretion of K+ by increasing the numbers of their channels.
Some organic materials produced and secreted by the salivary glands are mentioned earlier in the section on the functions of saliva. These materials include the enzymes αamylase (ptyalin) and lingual lipase, mucus, glycoproteins, lysozymes, and lactoferrin. Another enzyme produced by salivary glands is kallikrein, which converts a plasma protein into the potent vasodilator bradykinin. Kallikrein is released when the metabolism of the salivary glands increases; it is responsible in part for increased blood ﬂow to the secreting glands. Saliva also contains the blood group substances A, B, AB, and O. The synthesis of salivary gland enzymes, their storage, and their release are similar to the same processes in the pancreas. The protein concentration of saliva is approximately one tenth the concentration of proteins in the plasma.