The physiology of salivary secretion

Saliva in the mouth is a biofluid produced mainly by three pairs of major salivary glands--the submandibular, parotid and sublingual glands--along with secretions from many minor submucosal salivary glands. Salivary gland secretion is a nerve-mediated reflex and the volume of saliva secreted is dependent on the intensity and type of taste and on chemosensory, masticatory or tactile stimulation. Long periods of low (resting or unstimulated) flow are broken by short periods of high flow, which is stimulated by taste and mastication. The nerve-mediated salivary reflex is modulated by nerve signals from other centers in the central nervous system, which is most obvious as hyposalivation at times of anxiety. An example of other neurohormonal influences on the salivary reflex is the circadian rhythm, which affects salivary flow and ionic composition. Cholinergic parasympathetic and adrenergic sympathetic autonomic nerves evoke salivary secretion, signaling through muscarinic M3 and adrenoceptors on salivary acinar cells and leading to secretion of fluid and salivary proteins. Saliva gland acinar cells are chloride and sodium secreting, and the isotonic fluid produced is rendered hypotonic by salivary gland duct cells as it flows to the mouth. The major proteins present in saliva are secreted by salivary glands, creating viscoelasticity and enabling the coating of oral surfaces with saliva. Salivary films are essential for maintaining oral health and regulating the oral microbiome. Saliva in the mouth contains a range of validated and potential disease biomarkers derived from epithelial cells, neutrophils, the microbiome, gingival crevicular fluid and serum. For example, cortisol levels are used in the assessment of stress, matrix metalloproteinases-8 and -9 appear to be promising markers of caries and periodontal disease, and a panel of mRNA and proteins has been proposed as a marker of oral squamous cell carcinoma. Understanding the mechanisms by which components enter saliva is an important aspect of validating their use as biomarkers of health and disease.