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.     

Current cell models for bioengineering a salivary gland: a mini‐review of emerging technologies

Oral Diseases (2013) 19 , 236–244 Saliva plays a major role in maintaining oral health. Patients afflicted with a decrease in saliva secretion (symptomatically, xerostomia) exhibit difficulty in chewing and swallowing foods, tooth decay, periodontal disease, and microbial infections. Despite recent improvements in treating xerostomia (e.g., saliva stimulants, saliva substitutes, and gene therapy), there is a need of more scientific advancements that can be clinically applied toward restoration of compromised salivary gland function. Here we provide a summary of the current salivary cell models that have been used to advance restorative treatments via development of an artificial salivary gland. These models represent initial steps toward clinical and translational research, to facilitate creation of clinically safe salivary glands. Further studies in salivary cell lines and primary cells are necessary to improve survival rates, cell differentiation, and secretory function. Additionally, the characterization of salivary progenitor and stem cell markers are necessary. Although these models are not fully characterized, their improvement may lead to the construction of an artificial salivary gland that is in high demand for improving the quality of life of many patients suffering from salivary secretory dysfunction.     

The role of saliva in the oral defence mechanisms

Saliva plays an important role in oral health, regulating and maintaining the integrity of the oral hard tissues and soft tissues. This paper reviews the role of saliva in the oral defence mechanisms. The most important salivary immune and non-immune defence proteins and constituents that take part in the pellicle formation and re-mineralisation processes are introduced. General health conditions, medications and salivary gland disorders influencing the defence potential of the saliva are discussed. Treatment possibilities of such conditions, and the future perspective of saliva research is also presented.     

How much saliva is enough? 'Normal' function defined

Saliva is important for the preservation and maintenance of oral health. It is unclear, however, how much saliva is required to maintain normal oral function. Major salivary gland flow rates, objective measurements of oral health, and subjective complaints of oral problems were assessed in different-aged, healthy persons. Results suggest that the comparison of major salivary gland flow rates of an individual with population standards to identify patients susceptible to the effects of salivary dysfunction is unreliable. Changes in salivary function over time are a more meaningful gauge of the impact of saliva on oral health. The clinician should monitor salivary production to identify patients with declining salivary gland output.     

The rôle of saliva in maintaining oral health and as an aid to diagnosis

Saliva is a complex secretion. 93% by volume is secreted by the major salivary glands and the remaining 7% by the minor glands. 99% of saliva is water and the other 1% is composed of organic and inorganic molecules. While the quantity of saliva is important, so is its quality. The components of saliva, its functions in maintaining oral health and the main factors that cause alterations in salivary secretion will be reviewed, the importance of saliva in caries development and bacterial plaque formation will be discussed and its role as an aid to diagnosing certain pathologies will be examined. Variations in salivary flow can be affected, reversibly or irreversibly, by numerous physiological and pathological factors. Saliva plays an essential role in maintaining the integrity of the oral structures, in personal relationships, in the digestion and in controlling oral infection. The part that saliva plays in protecting teeth from caries can be summarised under four aspects: diluting and eliminating sugars and other substances, buffer capacity, balancing demineralisation/remineralisation and antimicrobial action. Saliva is a promising option for diagnosing certain disorders and monitoring the evolution of certain pathologies or the dosage of medicines or drugs. Its advantages as a diagnostic tool include its being easy to obtain and the positive correlation between many parameters in serum and saliva.     

Salivary gland disorders: A comprehensive review

Salivary glands are complex in nature. They could be either tubulo acinar, merocrine or exocrine glands secreting mainly saliva. Salivary gland is one of the main soft tissue structures in the maxillofacial area. Saliva is a clear, slightly acidic muco serous fluid that coats the teeth, mucosa and thereby helps to create and maintain a healthy environment in the oral cavity. Salivary glands may be affected by a number of diseases: local and systemic and the prevalence of salivary gland diseases depend on various etiological factors. The glands may be infected by viral, bacterial, rarely fungal or its ductal obstruction which may cause painful swelling or obstruction, affecting their functions. The salivary gland may also be affected by a various benign and malignant tumours. This review article briefly describes about the various salivary gland disorders, diagnostic techniques and their management including the recent advances and the future perspective.     

The diagnostic uses of saliva

It is becoming increasingly apparent to investigators and clinicians in a variety of disciplines that saliva has many diagnostic uses and is especially valuable in the young, the old and infirm and in large scale screening and epidemiologic studies. The highly sensitive test procedures that are now commonplace makes it practical to quantitate, despite very low concentrations, a large number of hormones and drugs in saliva. Indeed, all steroids of diagnostic significance in routine clinical endocrinology can now be readily measured in saliva. Drug monitoring can include abusive as well as therapeutic agents. The concordance between anti HIV antibodies in saliva and serum has stimulated application to various other antiviral antibodies as well as to viral antigens per se. Saliva has found use as a diagnostic aid in an increasing number of clinical situations and in systemic diseases that can affect salivary gland function and composition such as Sjögren's syndrome, cystic fibrosis and diseases of the adrenal cortex. The list keeps growing.     

Salivary gland function and changes in patients with oral lichen planus

Abstract – Saliva analysis, sialography and histopathologic examination of labial salivary glands were performed on patients with oral lichen planus. Diseases connected with salivary gland function were also recorded. Saliva analysis regarding secrection rate, pH and buffer capacity in unstimulated and stimulated saliva was permormed on 39 patients. 87% of the patients exhibired a low or very low unstimulated secretion rate, the mean value being 0.14 ml/min. The rate of stimulated saliva, pH and buffer capicity did not deviate from normal reference values. Sialographic examination was performed on 18 patients, corresponding to 36 major salivary glands. Radiologic changes were seen in 89% patients. Histopathologic examination was performed on 15 patients. Lymphocytic infiltration, acinar atrophy, fibrosis, fatty degeneration or ducral changes were observed in the minor glands of all patients. Different degrees of acinar atrophy were present in 93% of the patients. Lymphorytic infiltration was seen in 12 patients (80%) of whom three exhibited focal accumulation as in Sjögren's syndrome. Since decreased salivary secretion and symptoms of joint diseases and keratoconjunctivitis sicca were frequently present, over a third of the patients showed clinical signs comparable to those of Sjögren's syndrome. A high frequency of gastrointestinal and endocrine diseases was also recorded, which suggests that a general exo and endocrine influence may be present in patients with oral lichen planus.     

Non-neoplastic salivary gland diseases

A wide range of non neoplastic disorders can affect the salivary glands, although the more common are: mumps, acute suppurative sialadenitis, Sj?gren's syndrome and drug-induced xerostomia. Salivary dysfunction is not a normal consequence of old age, and can be due to systemic diseases, medications or head and neck radiotherapy. Diagnosis of salivary disorders begins with a careful medical history, followed by a cautious examination. While complaints of xerostomia may be indicative of a salivary gland disorder, salivary diseases can present without symptoms. Therefore, routine examination of salivary function must be part of any head, neck, and oral examination. Health-care professionals can play a vital role in identifying patients at risk for developing salivary dysfunction, and should provide appropriate preventive and interventive techniques that will help to preserving a person's health, function, and quality of life. The present work provides an overview of most of the non neoplastic disorders of the salivary glands, in which the general presentation, pathology, and treatments are discussed.     

Diagnosis and treatment of salivary gland disorders.

The keystone of the architecture of the oral cavity is saliva; however, it is rarely acknowledged as a vital physiologic secretion. Saliva plays three major roles in oral and systemic health. It provides host protection, assists in the initiation of food and fluid intake, and enables communication through speech. Without adequate salivary output augmented by a rich assortment of salivary proteins and electrolytes, oral and pharyngeal health declines as well as a person's quality of life. This article will provide a brief summary of the function of saliva, oral and systemic etiologies of salivary dysfunction, and methods to treat and prevent salivary disorders. Oral health care professionals can play a vital role in identifying patients at risk for developing salivary dysfunction and should provide appropriate preventive and interventive techniques that will help preserve oral health and function.     

Saliva and dental diseases.

Recent studies have greatly extended our understanding and appreciation of the various functions of saliva and its role in preventing dental disease. Elucidating the functions of the various salivary components as well as the mechanisms underlying normal salivary gland physiology is essential for developing rationales for the prevention and treatment of oral pathology. Individuals suffering from the consequences of a variety of forms of salivary gland dysfunction will benefit from therapies developed as the result of these advances. The application of relatively simple techniques for evaluating the functional status of salivary glands and salivary composition will aid in the identification of individuals most susceptible to oral disease.     

An update on minor salivary gland secretions

Eliasson L, Carlén A. An update on minor salivary gland secretions.
Eur J Oral Sci 2010; 118: 435–442. © 2010 Eur J Oral Sci In this article, the literature on minor salivary gland secretion rates, composition, and function is reviewed. Measurements of the minor salivary gland secretion rates and composition are complicated, and the secretions display large biological variability. Despite this, some characteristics of these secretions have been found repeatedly in independent investigations. Minor gland saliva varies between different oral sites. Buccal saliva flow is higher than labial saliva flow, which in turn is usually higher than the palatal gland secretion rate. It is generally agreed that minor gland saliva is important for the whole saliva composition, and especially for the secretory immunoglobulin A and mucins. The secretion from these glands seems also important for subjective feelings of dry mouth and general wellbeing. Further research is essential for understanding the role of these secretions for oral, as well as for general, health.     

Minor salivary gland secretion in children and adults

The minor salivary glands are of great importance in the physiology and pathology of the oral cavity. So far, studies of the minor glands have concentrated on adults. In the present study, minor salivary gland secretion was studied in the buccal and labial mucosa of 3-year-old children, adolescents and young adults. In addition, the number of glands per surface area was assessed in the labial mucosa. A total of 90 individuals were included, 30 in each age-group. Saliva was collected on filter paper discs and the salivary secretion rate was measured using a Periotron 8000. The number of secreting labial glands was assessed on PAS-stained filter paper discs under a microscope. Salivary secretion in the buccal mucosa was found to be age-related, with a statistically significant lower rate of secretion (P=0.003) in the 3-year-olds (mean 7.7 microl x cm(-2) x min(-1)) compared with the young adults (11.9 microl x cm(-2) x min(-1)). No significant differences between the sexes were noted. For the labial glands, no age- or sex-related differences were found. In all age-groups, salivary secretion was significantly higher in the buccal than in the labial mucosal area. A statistically significant difference in number of secreting glands was found between all age-groups, with a decreasing number of glands per surface unit with age. The number of glands was significantly lower in males compared with females in the group of adults. The lower rate of buccal salivary secretion in the young children may imply that the oral mucosa is more vulnerable to external injury and that caries protection on the buccal molar surfaces is lower. Previous studies indicate that adults with a reduced rate of minor salivary gland secretion are more susceptible to caries.     

Effects of hyperleptinemia in rat saliva composition,histology and ultrastructure of the major salivary glands

ObjectiveTo study the effect of the satiety hormone, leptin, in saliva proteome and salivary gland histology and ultrastructure.DesignIncreases in blood leptin levels were induced through mini-pump infusion in male Wistar rats, during a period of 7 days. Saliva was collected before and at the end of the experimental period, for proteomic analysis, and major salivary glands were collected, at the end, for biochemical, histological and ultrastructural analysis.ResultsImmunohistochemistry revealed the presence of leptin receptors in major salivary glands. Salivary amylase levels and enzymatic activity were decreased in saliva, whereas the enzymatic activity of this protein was increased in the cytosol of parotid gland cells. Transmission electron microscopy allowed the observation of high number of electron-dense granules in cytosol of parotid acinar cells, from leptin treated animals.ConclusionsIncreased levels of plasmatic leptin result in changes in saliva composition and salivary glands function. To our knowledge, this is the first study providing evidences for a potential role of leptin in salivary gland secretion and saliva composition. An understanding of how appetite/satiety factors influence saliva composition and how this composition influences food processing in mouth may be relevant in understanding ingestivebehaviour.     

Saliva secretion in engrafted mouse bioengineered salivary glands using taste stimulation

PurposeThe aim of this study was to compare saliva flow and protein composition induced using five basic taste stimulations between natural and bioengineered salivary glands.Materials and methodsWe developed a mouse saliva secretion model using taste stimulation and analyzed the saliva secretion from natural and bioengineered salivary glands using an assay. The protein components and alpha-amylase in the natural and bioengineered saliva were analyzed by gel electrophoresis and Western blotting.ResultsThe salivary flow responses induced by sour (citric acid) and bitter (quinine-HCl) stimuli were significantly high in the natural and bioengineered salivary glands. Although the protein concentrations in the natural and bioengineered saliva induced using five basic taste stimulations were similar, the protein composition and the amylase concentration in the natural saliva after taste stimulation had different profiles. Sympathetic and non-sympathetic nerves were observed around the acini and ducts in the natural and bioengineered salivary glands. However, the frequency of neuropeptide Y-positive sympathetic nerves in the bioengineered gland was relatively high compared to that in the natural gland.ConclusionsThese results suggest that the signal balance between the sympathetic and parasympathetic components of the efferent nerves in an engrafted bioengineered salivary gland may differ from that in a natural salivary gland.     

调控涎腺细胞分泌的受体及其信号转导的研究进展

涎腺细胞膜表面的受体及其所介导的信号转导通路是调控涎腺分泌的重要途径。本文概要介绍了毒蕈碱型胆碱受体、α1-肾上腺素受体、β-肾上腺素受体及辣椒素受体在正常颌下腺的表达及其对唾液分泌的调控作用,重点介绍了作者所进行的涎腺细胞受体对失神经支配的移植颌下腺分泌调控作用的研究结果。     

Effect of photic stimuli on rat salivary glands. Role of sympathetic nervous system

Saliva secretion during feeding facilitates chewing, swallowing and other oral functions. Between meals, a "resting saliva" is elicited to allow speaking and contribute to maintain soft and hard tissues health. Chewing is the main stimulus for "stimulated saliva" secretion. Mouth dryness and other less well known stimuli control "resting saliva". In humans the stimulus of the light increases the parotid saliva flow rate. Saliva secretion occurs in response to a reflex. Both motor branches of the autonomous nervous system drive efferent outputs to the salivary glands. Cellular bodies of sympathetic motor fibers innervating salivary glands are located in the superior cervical ganglia. A multisynaptic pathway couples the superior cervical ganglia to hypothalamic areas related to the control of autonomous and endocrine functions. Projections from suprachiasmatic nuclei involved in circadian rhythms control reach those areas. Salivary glands postsynaptic beta-adrenoceptors control synthesis and secretion of proteins. Postsynaptic alpha 2-adrenoceptors modulate salivary responses mediated by alpha 1 and beta-adrenoceptors. Parotid alpha-amylase circadian rhythm in suckling rats, suggest that the sympathetic nervous system mediates an effect of light on saliva secretion. Analysis of: 1) parotid fine structure, 2) submandibular secretory response to adrenergic agonists, and 3) submandibular 3H-clonidine binding to alpha 2-adrenoceptors, demonstrated that an increase of sympathetic reflex activity occurs in salivary glands of rats chronically exposed to constant light. Similar effects were observed in rats chronically exposed to immobilization stress. Catecholamine biosynthetic enzyme mRNA levels in adrenal glands and superior cervical ganglia suggest that changes induced by light on salivary sympathetic reflex activity are mediated by plasma catecholamines released by adrenal glands. Post and presynaptic alpha 2 adrenoceptors could play an important role in saliva secretion control when light or stress stimuli modify the sympathoadrenal system.     

Stimulated parotid salivary flow rate in patients with Down syndrome

Saliva is essential for oral defense against infections. Decreased salivary secretion may result in increased dental caries, oral mucosal changes, an altered sense of taste, difficulty in swallowing, and oral pain. A review of the literature reveals sporadic and contradictory reports on the use of sialometry and sialochemistry to explain the role of saliva in the oral health and well‐being of subjects with Down syndrome. The present study documents parotid gland saliva secretion at different ages in a group of subjects with Down syndrome. Saliva was collected from 39 patients 11 to 62 years old, by means of a parotid salivary gland cup and under standardized conditions of stimulated secretion. The rate of salivary secretion in the entire group of patients with Down syndrome was lower than that of healthy controls and lower in the older study group compared with the younger group. Institutionalized subjects or those living in hostellike apartments had a lower secretion rate than those living at home. No difference in salivary flow was found between those patients with Down syndrome with normal thyroid output and those with hypothyroidism who were receiving replacement therapy. In a four‐way ANOVA with flow as the dependent variable and Down syndrome, hypothyroidism, institutionalization, and age as factors, Down syndrome was found to be the only variable significantly related to flow (p = 0.017). Our findings indicate that stimulated parotid salivary hypofunction in Down syndrome subjects is mainly related to their genetic disorder.