Medical Physiology, 3rd Edition

Salivary Acinar Cell

Different salivary acinar cells secrete different proteins

The organizational structure of the salivary glands (Fig. 43-10A) is similar to that of the pancreas (see Fig. 43-1A), with secretory acinar units draining into progressively larger ducts. Unlike the pancreas, the salivary glands are heterogeneous in distribution and, in some species, contain two morphologically distinct acinar cell populations that synthesize and secrete different protein products. The acinar cells of the parotid glands in most species secrete a serous (i.e., watery) product that contains an abundance of α-amylase. Many acinar cells of the sublingual glands secrete a mucinous product that is composed primarily of mucin glycoproteins. Figure 43-10B shows an acinar cell that contains both serous and mucous granules. The submandibular gland of many species contains both mucous-type and serous-type acinar cells. In some species, these two distinct cell types are dispersed throughout the submandibular gland, whereas in other species such as humans, distinct mucous and serous acinar units are the rule. In addition to α-amylase and mucin glycoproteins, salivary acinar cells also secrete many proline-rich proteins. Like mucin proteins, proline-rich proteins are highly glycosylated, and like other secreted salivary proteins, they are present in the acinar secretory granules and are released by exocytosis.

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FIGURE 43-10 Salivary gland distribution and cellular morphology. A, Humans have three main bilateral salivary glands. The parotid glands are located in front of each ear, the submandibular glands are located laterally beneath each jaw bone, and the sublingual glands are located in the floor of the mouth, underneath both sides of the tongue.

Cholinergic and adrenergic neural pathways are the most important physiological activators of regulated secretion by salivary acinar cells

Unlike the pancreas, in which hormones have an important role in stimulating secretion, the salivary glands are mostly controlled by the autonomic nervous system (see Chapter 14). The major agonists of salivary acinar secretion are ACh and norepinephrine, which are released from postganglionic parasympathetic and sympathetic nerve terminals, respectively (see Fig. 14-8 and Table 43-4). The cholinergic receptor on the salivary acinar cell is the muscarinic M3 glandular subtype. The adrenergic receptors identified on these cells include both the α and β subtypes. Other receptors identified in salivary tissue include those for substance P (NK1 receptors), VIP, purinergic agonists (P2X7 receptors), neurotensin, prostaglandin, and epidermal growth factor (EGF). However, some of these other receptors are found only on specific salivary glands and may be present on duct cells rather than acinar cells. Significant species variation with regard to surface receptor expression is also seen. Thus, for the salivary glands, it is difficult to discuss the regulation of acinar cell secretion in general terms. It is fair to say, however, that both cholinergic and adrenergic neurotransmitters can stimulate exocytosis by salivary acinar cells.

TABLE 43-4

Autonomic Control of Salivary Secretion

AUTONOMIC PATHWAY

NEUROTRANSMITTER

RECEPTOR

SIGNALING PATHWAY

CELLULAR RESPONSE

Parasympathetic

ACh

Muscarinic (M3)

Ca2+

Fluid > protein secretion

Substance P

Tachykinin NK1

Ca2+

Fluid > protein secretion

Sympathetic

Norepinephrine

α-adrenergic

Ca2+

Fluid > protein secretion

Norepinephrine

β-adrenergic

cAMP

Protein ≫ fluid secretion

Both cAMP and Ca2+ mediate salivary acinar secretion

Protein secretion by the salivary acinar cell, as by the pancreatic acinar cell, is associated with increases in both [cAMP]i and [Ca2+]i. Activation of cAMP via the β-adrenergic receptor is the most potent stimulator of amylase secretion in the rat parotid gland. Activation of Ca2+ signaling pathways via the α-adrenergic, muscarinic, and substance P receptors also stimulates amylase secretion by the parotid gland, but in general, these Ca2+ signaling pathways have a greater effect on fluid secretion. Increases in [Ca2+]i cause G protein–dependent activation of PLC and thus lead to the formation of inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 releases Ca2+ from intracellular stores and stimulates Ca2+-dependent protein kinases such as PKC (see pp. 60–61) and calmodulin kinase (see p. 60), whereas DAG directly activates PKC (see pp. 60–61). The repetitive spikes in [Ca2+]i in salivary acinar cells, as in pancreatic acinar cells, depend on Ca2+-induced Ca2+ release from intracellular stores (see p. 60) and on the influx of extracellular Ca2+. ATP co-released with norepinephrine (see pp. 345–346) activates a P2X7 receptor, which is a ligand-gated cation-selective channel that allows Ca2+ to enter across the plasma membrane and thus increase [Ca2+]i.

Fluid and electrolyte secretion is the second major function of salivary acinar cells, accounting for ~90% of total salivary volume output under stimulatory conditions. The mechanisms in salivary acinar cells are similar to those in pancreatic acinar cells (see Fig. 43-5). The primary secretion of the salivary acinar cell is isotonic and results largely from the basolateral uptake of Cl through Na/K/Cl cotransporters, working in conjunction with Na-K pumps and basolateral K+ channels. Secretion of Cl and water into the lumen is mediated by apical Cl and aquaporin water channels. Na+ and some water reach the lumen via paracellular routes. The salivary acinar cells in some glands and species express carbonic anhydrase as well as parallel basolateral Cl-HCO3 exchangers (AE2) and Na-H exchangers (NHE1 and NHE4), as well as electrogenic Na/HCO3 cotransporters (NBCe1-B or SLC4A4; see p. 122). These acid-base transporters probably also contribute to the primary secretion.

Stimulation of fluid and electrolyte secretion by salivary acinar cells is largely mediated by cholinergic and α-adrenergic input. Substance P, acting through its own receptor, also initiates conductance changes in the salivary acinar cell. All these effects seem to be mediated by rises in [Ca2+]i. Apical Cl channels and basolateral K+ channels appear to be the effector targets of the activated Ca2+ signaling pathway. Phosphorylation of these channels by Ca2+-dependent kinases may affect the probability that these channels will be open and may thus increase conductance.