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Saliva and the Control of Its Secretion

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Dysphagia

Part of the book series: Medical Radiology ((Med Radiol Diagn Imaging))

Abstract

The various functions of saliva—among them digestive, protective, and trophic ones—not just limited to the mouth and the relative contribution of the different types of gland to the total volume secreted as well as to various secretory rhythms over time are discussed. Salivary reflexes, afferent and efferent pathways, as well as the action of classical and non-classical transmission mechanisms regulating the activity of the secretory elements and blood vessels are in focus. Sensory nerves of glandular origin and an involvement in gland inflammation are discussed. Although the glandular activities are principally regulated by nerves, recent findings of an “acute” influence of gastrointestinal hormones on saliva composition and metabolism are paid attention to, suggesting, in addition to the cephalic nervous phase both a regulatory gastric and intestinal phase. The influence of nerves and hormones in the long-term perspective as well as old age, diseases and consumption of pharmaceutical drugs on the glands and their secretion are discussed with focus on xerostomia and salivary gland hypofunction. Treatment options of dry mouth are presented as well as an explanation to the troublesome clozapine-induced sialorrhea. Final sections of this chapter describe the families of secretory salivary proteins and highlight the most recent results obtained in the study of the human salivary proteome. Particular emphasis is given to the post-translational modifications occurring to salivary proteins before and after secretion, to the polymorphisms observed in the different protein families and to the physiological variations, with a major concern to those detected in the paediatric age. Functions exerted by the different families of salivary proteins and the potential use of human saliva for prognostic and diagnostic purposes are finally discussed.

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References

  • Alajbeg I, Falcão DP, Tran SD, Martín-Granizo R, Lafaurie GI, Matranga D, Pejda S, Vuletíc L, Mantilla R, Leal SC, Bezerra ACB, Ménard HA, Kimoto S, Pan S, Maniegas L, Krushinski CA, Melilli D, Campisi G, Paderni C, Mendoza GRB, Yepes JF, Lindh L, Koray M, Mumcu G, Elad S, Zeevi I, Barrios BCA, Sànchez RML, Lassauuzay C, Fromentin O, Beiski BZ, Strietzel FP, Konttinen YT, Wolff A, Zunt SI (2012) Intraoral electrostimulator for xerostomia relief: a long-term, multicenter, open-label, uncontrolled, clinical trial. Oral Surg Oral Med Oral Pathol Oral Radiol 113:773–781

    Article  PubMed  Google Scholar 

  • Arba M, Iavarone F, Vincenzoni F, Manconi B, Vento G, Tirone C, Cabras T, Castagnola M, Messana I, Sanna MT (2016) Proteomic characterization of the acid-insoluble fraction of whole saliva from preterm human newborns. J Proteome 146:48–57

    Article  CAS  Google Scholar 

  • Asztély A, Havel G, Ekström J (1998) Vascular protein leakage in the rat parotid gland elicited by reflex stimulation, parasympathetic nerve stimulation and administration of neuropeptides. Regul Pept 77:113–120

    Article  PubMed  Google Scholar 

  • Atkinson JC, Shiroky JB, Macynski A, Fox PC (1989) Effects of furosemide on the oral cavity. Gerodontology 8:23–26

    Article  PubMed  CAS  Google Scholar 

  • Bobek LA, Levine MJ (1992) Cystatins--inhibitors of cysteine proteinases. Crit Rev Oral Biol Med 3:307–332

    Article  PubMed  CAS  Google Scholar 

  • Bobek LA, Liu J, Sait SN, Shows TB, Bobek YA, Levine MJ (1996) Structure and chromosomal localization of the human salivary mucin gene, MUC7. Genomics 31:277–282

    Article  PubMed  CAS  Google Scholar 

  • Babkin BP (1950) Secretory mechanism of the digestive glands, 2nd edn. Paul B Hoeber, New York

    Google Scholar 

  • Barka T (1965) Induced cell proliferation: the effect of isoproterenol. Exp Cell Res 37:662–679

    Article  PubMed  CAS  Google Scholar 

  • Birkhed D, Heintze U (1989) Salivary secretion rate, buffer capacity, and pH. In: Tenovuo J (ed) Human saliva: clinical chemistry and microbiology, vol 11. CRC Press, Boca Raton, FL

    Google Scholar 

  • Blair-West JR, Coghlan JP, Denton DA, Wright RDI (1967) In: Code CF (ed) Handbook of physiology, Alimentary Canal II, 6th edn. Betheshda, Washington, American Physiological Society

    Google Scholar 

  • Borg-Andersson A, Ekström J, Birkhed D (1992) Glucose in human parotid saliva in response to cold stress. Acta Physiol Scand 146:283–284

    Article  PubMed  CAS  Google Scholar 

  • Brandtzaeg P (2009) Mucosal immunity: induction, dissemination, and effector functions. Scand J Immunol 70:505–515

    Article  PubMed  CAS  Google Scholar 

  • Cabras T, Boi R, Pisano E, Iavarone F, Fanali C, Nemolato S, Faa G, Castagnola M, Messana I (2012a) HPLC-ESI-MS and MS/MS structural characterization of multifucosylated N-glycoforms of the basic proline-rich protein IB-8a CON1+ in human saliva. J Sep Sci 35:1079–1086

    Article  PubMed  CAS  Google Scholar 

  • Cabras T, Fanali C, Monteiro JA, Amado F, Inzitari R, Desiderio C, Scarano E, Giardina B, Castagnola M, Messana I (2007) Tyrosine polysulfation of human salivary histatin 1. A post-translational modification specific of the submandibular gland. J Proteome Res 6:2472–2480

    Article  PubMed  CAS  Google Scholar 

  • Cabras T, Melis M, Castagnola M, Padiglia A, Tepper BJ, Messana I, Tomassini Barbarossa I (2012b) Responsiveness to 6-n-Propylthiouracil (PROP) is associated with salivary levels of two specific basic Proline-rich proteins in humans. PLoS One 7:e30962

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cabras T, Pisano E, Boi R, Olianas A, Manconi B, Inzitari R, Fanali C, Giardina B, Castagnola M, Messana I (2009) Age-dependent modifications of the human salivary secretory protein complex. J Proteome Res 8:4126–4134

    Article  PubMed  CAS  Google Scholar 

  • Cannon WB (1937) Digestion and health. Secker & Warburg, London

    Google Scholar 

  • Castagnola M, Inzitari R, Rossetti DV, Olmi C, Cabras T, Piras V, Nicolussi P, Sanna MT, Pellegrini M, Giardina B, Messana I (2004) A cascade of 24 histatins (histatin 3 fragments) in human saliva. Suggestions for a pre-secretory sequential cleavage pathway. J Biol Chem 279:41436–41443

    Article  PubMed  CAS  Google Scholar 

  • Castagnola M, Inzitari R, Fanali C, Iavarone F, Vitali A, Desiderio C, Vento G, Tirone C, Romagnoli C, Cabras T, Manconi B, Sanna MT, Boi R, Pisano E, Olianas A, Pellegrini M, Nemolato S, Heizmann CW, Faa G, Messana I (2011a) The surprising composition of the salivary proteome of preterm human newborn. Mol Cell Proteomics 10:M110.003467

    Article  PubMed  CAS  Google Scholar 

  • Castagnola M, Cabras T, Vitali A, Sanna MT, Messana I (2011b) Biotechnological implication of the salivary proteome. Trends Biotechnol 29:409–418

    Article  PubMed  CAS  Google Scholar 

  • Castagnola M, Scarano E, Passali GC, Messana I, Cabras T, Iavarone S, Di Cintio G, Fiorita A, De Corso E, Paludetti G (2017) Salivary biomarkers and proteomics: future diagnostic and clinical utilities. Acta Otorhinolaryngol Ital 37:94–101

    PubMed  PubMed Central  CAS  Google Scholar 

  • Çevik-Aras H, Ekström J (2006) Cholecystokinin- and gastrin-induced protein and amylase secretion from the parotid gland of the anaesthetized rat. Regul Pept 134:89–96

    Article  CAS  Google Scholar 

  • Çevik-Aras H, Ekström J (2008) Melatonin-evoked in vivo secretion of protein and amylase from the parotid gland of the anaesthetized rat. J Pineal Res 45:413–421

    Article  CAS  Google Scholar 

  • Çevik-Aras H, Ekström J (2010) Anti-inflammatory action of cholecystokinin and melatonin in the rat parotid gland. Oral Dis 16:661–667

    Article  PubMed  Google Scholar 

  • Çevik-Aras H, Godoy T, Ekström J (2011) Melatonin-induced protein synthesis in the rat parotid gland. J Physiol Pharmacol 62:95–99

    PubMed  Google Scholar 

  • Chen YC, Li TY, Tsai MF (2002) Analysis of the saliva from patients with oral cancer by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Rapid Commun Mass Spectrom 16:364–369

    Article  PubMed  CAS  Google Scholar 

  • Cuevas-Córdoba B, Santiago-García J (2014) Saliva: a fluid of study for OMICS. OMICS 18:87–97

    Article  PubMed  CAS  Google Scholar 

  • Cutando A, Gómez-Moreno G, Arana C, Acuña-Castroviejo D, Reiter RJ (2007) Melatonin: potential functions in the oral cavità. J Periodontol 78:1094–1194

    Article  PubMed  Google Scholar 

  • Dawes C (1975) Circadian rhythms in the flow rate and composition of unstimulated and stimulated human submandibular saliva. J Physiol 244:535–548

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dawes C (2003) Estimates, from salivary analyses, of the turnover time of the oral mucosal epithelium in humans and the number of bacteria in an edentulous mouth. Arch Oral Biol 48:329–336

    Article  PubMed  CAS  Google Scholar 

  • Dawes C (1987) Physiological factors affecting salivary flow rate, oral sugar clearance, and the sensation of dry mouth. J Dent Res 66:648–653

    Article  PubMed  Google Scholar 

  • Dawes C, Pedersen AML, Villa A, Ekström J, Proctor GB, Vissink A, Aframian D, McGowan R, Aliko A, Narayama N, Sia YW, Joshi RK, Jensen SB, Kerr AR, Wolff A (2015) The functions of human saliva: a review sponsored by the world workshop on oral medicine VI. Arch Oral Biol 60:863–874

    Article  PubMed  CAS  Google Scholar 

  • Dawes C, O'Connor AM, Aspen JM (2000) The effect on human salivary flow rate of the temperature of a gustatory stimulus. Arch Oral Biol 45:957–961

    Article  PubMed  CAS  Google Scholar 

  • Dawes C, Wood CM (1973) The contribution of oral minor mucous gland secretions to the volume of whole saliva in man. Arch Oral Biol 18:337–342

    Article  PubMed  CAS  Google Scholar 

  • Del Fiacco M, Quartu M, Ekström J, Melis T, Boi M, Isola M, Loy F, Serra MP (2015) Effect of the neuropeptides vasoactive intestinal peptide, peptide histidine methionine and substance P on human salivary gland secretion. Oral Dis 21:216–223

    Article  PubMed  Google Scholar 

  • de Jong EP, Xie H, Onsongo G, Stone MD, Chen XB, Kooren JA, Refsland EW, Griffin RJ, Ondrey FG, Wu B, Le CT, Rhodus NL, Carlis JV, Griffin TJ (2010) Quantitative proteomics reveals myosin and actin as promising saliva biomarkers for distinguishing pre-malignant and malignant oral lesions. PLoS One 5:e11148

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Diamant H, Wiberg A (1965) Does the chorda tympani in man contain secretory fibres for the parotid gland? Acta Otolaryngol 60:255–264

    Article  Google Scholar 

  • Dickinson DP (2002) Cysteine peptidases of mammals: their biological roles and potential effects in the oral cavity and other tissues in health and disease. Crit Rev Oral Biol Med 13:238–275

    Article  PubMed  CAS  Google Scholar 

  • DiSabato-Mordaski T, Kleinberg I (1996) Measurement and comparison of the residual saliva on various oral mucosal and dentition surfaces in humans. Arch Oral Biol 41:655–665

    Article  Google Scholar 

  • Douglas WH, Reeh ES, Ramasubbu N, Raj PA, Bhandary KK, Levine MJ (1991) Statherin: a major boundary lubricant of human saliva. Biochem Biophys Res Commun 180:91–97

    Article  PubMed  CAS  Google Scholar 

  • Dowling P, Wormald R, Meleady P, Henry M, Curran A, Clynes M (2008) Analysis of the saliva proteome from patients with head and neck squamous cell carcinoma reveals differences in abundance levels of proteins associated with tumour progression and metastasis. J Proteome 71:168–175

    Article  CAS  Google Scholar 

  • Drummond PD (2002) Mechanisms of gustatory flushing in Frey’s syndrome. Clin Auton Res 12:179–184

    Article  Google Scholar 

  • Dunbar EM, Singer TW, Singer K, Knight H, Lanska D, Okun MS (2002) Understanding gustatory sweating. What have we learned from Lucja Frey and her predecessors? Clin Auton Res 12:179–184

    Article  PubMed  Google Scholar 

  • Ecobichon DJ (1995) Toxic effects of pesticides. In: Klassen CD (ed) Casarett & Doulll’s toxicology. The basic science of poisons, 5th edn. McGraw- Hill, New York

    Google Scholar 

  • Edwards AV (1988) Autonomic control of salivary blood flow. In: Garrett JR, Ekström J, Anderson LC (eds) Glandular mechanisms of salivary secretion. Frontiers of oral biology, vol 10. Karger, Basel

    Google Scholar 

  • Ekström J (1969) 4(2-hydroxy-3-isopropylaminopropoxy) acetanilide as a beta-receptor blocking agent. Experientia 25:372

    Article  PubMed  Google Scholar 

  • Ekström J (1987) Neuropeptides and secretion. J Dent Res 66:524–530

    Article  PubMed  Google Scholar 

  • Ekström J (1998) Non-adrenergic, non-cholinergic reflex secretion of parotid saliva in rats elicited by mastication and acid applied on the tongue. Exp Physiol 83:697–700

    Article  PubMed  Google Scholar 

  • Ekström J (1999a) Role of non-adrenergic, non-cholinergic autonomic transmitters in salivary glandular activities in vivo. In: Garrett JR, Ekström J, Anderson LC (eds) Neural mechanisms of salivary gland secretion. Frontiers of oral biology, vol 11. Karger, Basel

    Google Scholar 

  • Ekström J (1999b) Degeneration secretion and supersensitivity in salivary glands following denervations, and the effects on choline acetyltransferase activity. In: Garrett JR, Ekström J, Anderson LC (eds) Neural mechanisms of salivary gland secretion. Frontiers of oral biology, vol 11. Karger, Basel

    Google Scholar 

  • Ekström J (2001) Gustatory-salivary reflexes induce non-adrenergic, non-cholinergic acinar degranulation in the rat parotid gland. Exp Physiol 86:475–480

    Article  PubMed  Google Scholar 

  • Ekström J (2002) Muscarinic agonist-induced non-granular and granular secretion of amylase in the parotid gland of the anaesthetized rat. Exp Physiol 87:147–152

    Article  PubMed  Google Scholar 

  • Ekström J, Çevik Aras H (2008) Parasympathetic non-adrenergic, non-cholinergic transmission in rat parotid glands: effects of cholecystokinin-a and -B receptor antagonists on the secretory response. Regul Pept 146:278–284

    Article  PubMed  CAS  Google Scholar 

  • Ekström J, Çevik-Aras H, Sayardoust S (2007) Neural- and hormonal-induced protein synthesis and mitotic activity in the rat parotid gland and the dependence on NO-generation. J Oral Biosci 49:31–38

    Article  Google Scholar 

  • Ekström J, Ekman R (2005) Sympathectomy-induced increases in calcitonin gene-related peptide (CGRP)-, substance P- and vasoactive intestinal peptide (VIP)-levels in parotid and submandibular glands of the rat. Arch Oral Biol 50:909–917

    Article  PubMed  CAS  Google Scholar 

  • Ekström J, Ekman R, Håkanson R, Sjögren S, Sundler F (1988) Calcitonin gene-related peptide in rat salivary glands: neuronal localization, depletion upon nerve stimulation, and effects on salivation in relation to substance P. Neuroscience 26:933–949

    Article  PubMed  Google Scholar 

  • Ekström J, Ekman R, Luts A, Sundler F, Tobin G (1996) Neuropeptide Y in salivary glands of the rat: origin, release and secretory effects. Regul Pept 61:125–134

    Article  PubMed  Google Scholar 

  • Ekström J, Engdahl Havel G, Reinhold A-C (2000) Parasympathetic non-adrenergic, non-cholinergic-induced protein synthesis and mitogenic activity in rat parotid glands. Exp Physiol 85:171–176

    Article  PubMed  Google Scholar 

  • Ekström J, Godoy T, Riva A (2010a) Clozapine: agonistic and antagonistic salivary secretory actions. J Dent Res 89:276–280

    Article  PubMed  CAS  Google Scholar 

  • Ekström J, Godoy T, Riva A (2010b) N-Desmethylclozapine exerts dual and opposite effects on salivary secretion in the rat. Eur J Oral Sci 118:1–8

    Article  PubMed  Google Scholar 

  • Ekström J, Godoy T, Loy F, Riva A (2014) Parasympathetic vasoactive intestinal peptide (VIP): a likely contributor to clozapine-induced sialorrhea. Oral Dis 20:e90–e96

    Article  PubMed  Google Scholar 

  • Ekström J, Holmberg J (1972) Choline acetyltransferase in the normal and parasympathetically denervated parotid gland of the dog. Acta Physiol Scand 86:353–358

    Article  PubMed  Google Scholar 

  • Ekström J, Malmberg L (1984) Beta 1-adrenoceptor mediated salivary gland enlargement in the rat. Experientia 40:862–863

    Article  PubMed  Google Scholar 

  • Ekström J, Murakami M, Inzitari R, Khosravani N, Fanali C, Cabras T, Fujita-Yoshigaki J, Sugiya H, Messana I, Castagnol M (2009) RP-HPLC-ESI-MS characterization of novel peptide fragments related to rat parotid secretory protein in parasympathetic induced saliva. J Sep Sci 32:2944–2952

    Article  PubMed  CAS  Google Scholar 

  • Ekström J, Reinhold AC (2001) Reflex-elicited increases in female rat parotid protein synthesis involving parasympathetic non-adrenergic, non-cholinergic mechanisms. Exp Physiol 86:605–610

    Article  PubMed  Google Scholar 

  • Ekström J, Templeton D (1977) Difference in sensitivity of parotid glands brought about by disuse and overuse. Acta Physiol Scand 101:329–335

    Article  PubMed  Google Scholar 

  • Eliasson L, Birkhed D, Heyden G, Strömberg N (1996) Studies on human minor salivary gland secretion using the Periotron method. Arch Oral Biol 41:1179–1182

    Article  PubMed  CAS  Google Scholar 

  • Eliasson L, Carlén A (2010) An update on minor salivary gland secretions. Eur J Oral Sci 118:435–442

    Article  PubMed  Google Scholar 

  • Elishoov H, Wolff A, Kravel LS, Shiperman A, Gorsky M (2008) Association between season and temperature and unstimulated parotid and submandibular/sublingual secretion rates. Arch Oral Biol 53:75–78

    Article  PubMed  CAS  Google Scholar 

  • Emmelin N (1965) Action of transmitters on the responsiveness of effector cells. Experientia 15:57–65

    Article  Google Scholar 

  • Emmelin N (1967) Nervous control of salivary glands. In: Code CF (ed) Handbook of physiology, Alimentary Canal II, 6th edn. Betheshda, Washington, American Physiological Society

    Google Scholar 

  • Emmelin N (1987) Nerve interactions in salivary glands. J Dent Res 66:509–517

    Article  PubMed  CAS  Google Scholar 

  • Emmelin N, Engström J (1960) On the existence of specific secretory sympathetic fibres for the cat's submaxillary gland. J Physiol 153:1–8

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Engeland CG, Hugo FN, Hilgert JB, Nascimento CG, Junges R, Lim H-J, Marucha PT, Bosch JA (2016) Psychological distress and salivary secretory immunity. Brain Behav Immun 52:11–17

    Article  PubMed  CAS  Google Scholar 

  • Ericsson Y, Hardwick L (1978) Individual diagnosis, prognosis and counseling for caries prevention. Caries Res 12:94–102

    Article  PubMed  Google Scholar 

  • Ferguson DB, Botchway CA (1980) A comparison of circadian variation in the flow rate and composition of stimulated human parotid, submandibular and whole salivas from the same individuals. Arch Oral Biol 25:559–568

    Article  PubMed  CAS  Google Scholar 

  • Field EA, Longman LP, Bucknall R, Kaye SB, Higham SM, Edgar WM (1997) The establishment of a xerostomia clinic: a prospective study. Br J Oral Maxiofac Surg 35:96–103

    Article  CAS  Google Scholar 

  • Fleissig Y, Deutsch O, Reichenberg E, Redlich M, Zaks B, Palmon A, Aframian DJ (2009) Different proteomic protein patterns in saliva of Sjögren's syndrome patients. Oral Dis 15:61–68

    Article  PubMed  CAS  Google Scholar 

  • Freudenreich O (2005) Drug-induced sialorrhea. Drugs Today (Barc) 41:411–418

    Article  CAS  Google Scholar 

  • Gallacher DV, Smith PM (1999) Autonomic transmitters and Ca2+ −activated cellular responses in salivary glands in vitro. In: Garrett JR, Ekström J, Anderson LC (eds) Neural mechanisms of salivary gland secretion. Frontiers of oral biology, vol 11. Karger, Basel

    Google Scholar 

  • Garrett JR (1988) Innervation of salivary glands: neurohistological and functional aspects. In: Sreebny LM (ed) The salivary system. CRC Press, Boca Raton, FL

    Google Scholar 

  • Garrett JR (1998) Historical introduction to salivary secretion. In: Garrett JR, Ekström J, Anderson LC (eds) Glandular mechanisms of salivary secretion. Frontiers of oral biology, vol 10. Karger, Basel

    Chapter  Google Scholar 

  • Garrett JR, Emmelin N (1979) Activities of salivary myoepithelial cells: a review. Med Biol 57:1–28

    PubMed  CAS  Google Scholar 

  • Garrett JR, Thulin A (1975) Changes in parotid acinar cells accompanying salivary secretion in rats on sympathetic or parasympathetic nerve stimulation. Cell Tiss Res 159:179–193

    Article  CAS  Google Scholar 

  • Gendler SJ, Spicer AP (1995) Epithelial mucin genes. Annu Rev Physiol 57:607–634

    Article  PubMed  CAS  Google Scholar 

  • Gibbons RJ, Hay DI (1988) Human salivary acidic proline-rich proteins and statherin promote the attachment of Actinomyces Viscosus LY7 to apatitic surfaces. Infect Immun 56:439–445

    PubMed  PubMed Central  CAS  Google Scholar 

  • Gorr S-U (2009) Antimicrobial peptides of the oral cavity. Periodontol 2000(51):152–180

    Article  Google Scholar 

  • Giusti L, Baldini C, Bazzichi L, Ciregia F, Tonazzini I, Mascia G, Giannaccini G, Bombardieri S, Lucacchini A (2007) Proteome analysis of whole saliva: a new tool for rheumatic diseases – the example of Sjögren's syndrome. Proteomics 7:1634–1643

    Article  PubMed  CAS  Google Scholar 

  • Godoy T, Riva A, Ekström J (2011) Clozapine-induced salivation: interaction with N-desmethylclozapine and amisulpride in an experimental rat model. Eur J Oral Sci 119:275–281

    Article  PubMed  CAS  Google Scholar 

  • Godoy T, Riva A, Ekström J (2012) Atypical antipsychotics – effects of amisulpride on salivary secretion and on clozapine-induced sialorrhea. Oral Dis 18:680–691

    Article  PubMed  CAS  Google Scholar 

  • Gomes GP, Assis MA, Fonseca JS, de Souza PE, Zenóbio EG, Oliveira DD, Soares RV (2011) Genetic polymorphism of MUC7 in individuals with aggressive or chronic periodontitis. J Oral Sci 53:445–449

    Article  PubMed  CAS  Google Scholar 

  • Gorr SU, Venkatesh SG, Darling DS (2005) Parotid secretory granules: crossroads of secretory pathways and protein storage. J Dent Res 84:500–509

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gray H (1988) Gray’s anatomy: the classical Collector’s edition. Bounty Books, New York

    Google Scholar 

  • Gregersen MI (1931) A method for uniform stimulation of the salivary glands in the unaesthetized dog by exposure to a warm environment, with some observations on the quantitative changes in salivary flow during dehydration. Am J Phys 97:107–116

    Google Scholar 

  • Grisius MM, Fox PC (1988) Salivary gland dysfunction and xerostomia. In: Linden RWA (ed) The scientific basis of eating. Frontiers of oral biology, vol 9. Karger, Basel

    Google Scholar 

  • Gröschl M (2009) The physiological role of hormones in saliva. BioEssays 31:843–852

    Article  PubMed  CAS  Google Scholar 

  • Guile GR, Harvey DJ, O'Donnell N, Powell AK, Hunter AP, Zamze S, Fernandes DL, Dwek RA, Wing DR (1998) Identification of highly fucosylated N-linked oligosaccharides from the human parotid gland. Eur J Biochem 258:623–656

    Article  PubMed  CAS  Google Scholar 

  • Hainsworth RF (1967) Saliva spreading, activity, and body temperature regulation in the rat. Am J Phys 212:1288–1292

    CAS  Google Scholar 

  • Halgand F, Zabrouskov V, Bassilian S, Souda P, Loo JA, Faull KF, Wong DT, Whitelegge JP (2012) Defining intact protein primary structures from saliva: a step toward the human proteome project. Anal Chem 84:4383–4395

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Halgand F, Zabrouskov V, Bassilian S, Souda P, Wong DT, Loo JA, Faull KF, Whitelegge JP (2010) Micro-heterogeneity of human saliva peptide P-C characterized by high-resolution top-down Fourier-transform mass spectrometry. J Am Soc Mass Spectr 21:868–877

    Article  CAS  Google Scholar 

  • Hector MP, Linden RWA (1999) Reflexes of salivary secretion. In: Garrett JR, Ekström J, Andersson LC (eds) Neural mechanisms of salivary glands. Frontiers of oral biology, vol 11. Karger, Basel

    Google Scholar 

  • Heintze U, Birkhed D, Björn H (1983) Secretion rate and buffer effect of resting and stimulated whole saliva as a function of age and sex. Swed Dent J 7:227–238

    PubMed  CAS  Google Scholar 

  • Helm JF, Dodds WJ, Hogan WJ (1987) Salivary response to esophageal acid in normal subjects and patients with reflux esophagitis. Gastroenterology 93:1393–1397

    Article  PubMed  CAS  Google Scholar 

  • Helmerhorst EJ, Sun X, Salih E, Oppenheim FG (2008) Identification of Lys-pro-Gln as a novel cleavage site specificity of saliva-associated proteases. J Biol Chem 283:19957–19966

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hsu CW, Yu JS, Peng PH, Liu SC, Chang YS, Chang KP, Wu CC (2014) Secretome profiling of primary cells reveals that THBS2 is a salivary biomarker of oral cavity squamous cell carcinoma. J Proteome Res 13:4796–4807

    Article  PubMed  CAS  Google Scholar 

  • Hu S, Arellano M, Boontheung P, Wang J, Zhou H, Jiang J, Elashoff D, Wei R, Loo JA, Wong DT (2008) Salivary proteomics for oral cancer biomarker discovery. Clin Cancer Res 14:6246–6252

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Huang CM, Torpey JW, Liu YT, Chen YR, Williams KE, Komives EA, Gallo RL (2008) A peptide with a ProGln C terminus in the human saliva peptidome exerts bactericidal activity against Propionibacterium acnes. Antimicrob Agents Chemother 52:1834–1836

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Iavarone F, D'Alessandro A, Tian N, Cabras T, Messana I, Helmerhorst EJ, Oppenheim FG, Castagnola M (2014) High-resolution high-performance liquid chromatography with electrospray ionization mass spectrometry and tandem mass spectrometry characterization of a new isoform of human salivary acidic proline-rich proteins named Roma-Boston Ser22 (Phos) → Phe variant. J Sep Sci 37:1896–1902

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Imai A, Nashida T, Shimomura H (1995) Regulation of cAMP phosphodiesterases by cyclic nucleotids in rat parotid gland. Biochem Mol Biol Int 37:1029–1036

    PubMed  CAS  Google Scholar 

  • Imamura Y, Fujigaki Y, Oomori Y, Usui S, Wang PL (2009) Cooperation of salivary protein histatin 3 with heat shock cognate protein 70 relative to the G1/S transition in human gingival fibroblasts. J Biol Chem 284:14316–14325

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Inzitari R, Cabras T, Onnis G, Olmi C, Mastinu A, Sanna MT, Pellegrini MG, Castagnola M, Messana I (2005) Different isoforms and post-translational modifications of human salivary acidic proline-rich proteins. Proteomics 5:805–815

    Article  PubMed  CAS  Google Scholar 

  • Inzitari R, Cabras T, Rossetti DV, Fanali C, Vitali A, Pellegrini M, Paludetti G, Manni A, Giardina B, Messana I, Castagnola M (2006) Detection in human saliva of different statherin and P-B fragments and derivatives. Proteomics 6:6370–6379

    Article  PubMed  CAS  Google Scholar 

  • Inzitari R, Cabras T, Pisano E, Fanali C, Manconi B, Scarano E, Fiorita A, Paludetti G, Manni A, Nemolato S, Faa G, Castagnola M, Messana I (2009) HPLC-ESI-MS analysis of oral human fluids reveals that gingival crevicular fluid is the main source of oral thymosins beta(4) and beta(10). J Sep Sci 32:57–63

    Article  PubMed  CAS  Google Scholar 

  • Isenman L, Liebow C, Rothman S (1999) The endocrine secretion of mammalian digestive enzymes by exocrine glands. Am J Phys 276:E223–E232

    CAS  Google Scholar 

  • Isola M, Ekström J, Diana M, Solinas P, Cossu M, Lilliu MA, Loy F, Isola R (2013) Subcellular distribution of melatonin receptors in human parotid glands. J Anat 223:519–524

    PubMed  PubMed Central  CAS  Google Scholar 

  • Isola M, Lilliu MA (2016) Melatonin localization in human salivary glands. J Oral Pathol Med 45:510–515

    Article  PubMed  CAS  Google Scholar 

  • Isola M, Ekström J, Lilliu MA, Isola R, Loy F (2016) Dynamics of the melatonin MT1 receptor in the rat parotid gland upon melatonin administration. J Physiol Pharmacol 67:111–119

    PubMed  CAS  Google Scholar 

  • Jenkins GN (1978) The physiology and biochemistry of the mouth. Blackwell Scientific Publications, Oxford

    Google Scholar 

  • Jensen Kjeilen JC, Brodin P, Aars H, Berg T (1987) Parotid salivary flow in response to mechanical and gustatory stimulation in man. Acta Physiol Scand 131:169–175

    Article  PubMed  CAS  Google Scholar 

  • Jessie K, Jayapalan JJ, Ong KC, Abdul Rahim ZH, Zain RM, Wong KT, Hashim OH (2013) Aberrant proteins in the saliva of patients with oral squamous cell carcinoma. Electrophoresis 34:2495–2502

    Article  PubMed  CAS  Google Scholar 

  • Johanson CN, Österberg T, Lernfelt B, Ekström J, Birkhed D (2015) Salivary secretion and drug treatment in four 70-year-old Swedish cohorts during a period of 30 years. Gerodontology 32:202–210

    Article  PubMed  Google Scholar 

  • Johnson DA (1988) Regulation of salivary glands and their secretion by masticatory, nutritional and hormonal factors. In: Sreebny LM (ed) The salivary system. CRC Press, Boca Raton, FL

    Google Scholar 

  • Jou YJ, Lin CD, Lai CH, Chen CH, Kao JY, Chen SY, Tsai MH, Huang SH, Lin CW (2010) Proteomic identification of salivary transferrin as a biomarker for early detection of oral cancer. Anal Chim Acta 681:41–48

    Article  PubMed  CAS  Google Scholar 

  • Jou YJ, Hua CH, Lin CD, Lai CH, Huang SH, Tsai MH, Kao JY, Lin CW (2014) S100A8 as potential salivary biomarker of oral squamous cell carcinoma using nanoLCMS/MS. Clin Chim Acta 436:121–129

    Article  PubMed  CAS  Google Scholar 

  • Kariyawasam AP, Dawes C (2005) A circannual rhythm in unstimulated salivary flow rate when the ambient temperature varies by only about 2 degrees C. Arch Oral Biol 50:919–922

    Article  PubMed  CAS  Google Scholar 

  • Khadivi E, Zadeh FA, Bakhshae M, Fooladvand T, Movahed SR, Nabavi SS, Aghaee MA (2013) Bilateral submandibular duct rerouting: assessment of results on drooling in cerebral palsy cases. Ausis Nasus Larynx 40:487–490

    Article  Google Scholar 

  • Khosravani N, Ekman R, Ekström J (2008) The peptidergic innervations of the rat parotid gland. Effects of section of the auriculo-temporal nerve and/or otic ganglionectomy. Arch Oral Biol 53:238–242

    Article  PubMed  CAS  Google Scholar 

  • Khosravani N, Birkhed D, Ekström J (2009) The cholinesterase inhibitor physostigmine for the local treatment of dry mouth: a randomized study. Eur J Oral Sci 117:209–217

    Article  PubMed  CAS  Google Scholar 

  • Khosravani N, Sandberg M, Ekström J (2006) The otic ganglion in rats and its parotid connection: cholinergic pathways, reflex secretion and a secretory role for the facial nerve. Exp Physiol 91:239–247. Erratum in: Exp Physiol 2006;91:481

    Article  PubMed  Google Scholar 

  • Khosravani N, Ekström J (2006) Facial nerve section induces transient changes in sensitivity to methacholine and in acetylcholine synthesis in the rat parotid gland. Arch Oral Biol 51:736–739

    Article  PubMed  CAS  Google Scholar 

  • Lee MG, Lee YH (2015) A meta-analysis examining the association between the MUC5B rs35705950 T/G polymorphism and susceptibility to idiopathic pulmonary fibrosis. Inflamm Res 64:463–470

    Article  PubMed  CAS  Google Scholar 

  • Leipzig B, Obert P (1979) Parotid gland swelling. J Fam Pract 9:1085–1093

    PubMed  CAS  Google Scholar 

  • Lombaert I, Movahednia MM, Adine C, Ferreira JN (2017) Concise review: salivary gland regeneration: therapeutic approaches from stem cells to tissue organoids. Stem Cells 35:97–105

    Article  PubMed  CAS  Google Scholar 

  • Loo JA, Yan W, Ramachandran P, Wong DT (2010) Comparative human salivary and plasma proteomes. J Dent Res 89:1016–1023

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Longman LP, Higham SM, Rai K, Edgar WM, Field EA (1995) Salivary gland hypofunction in elderly patients attending a xerostomic clinic. Gerodontology 12:67–72

    Article  PubMed  CAS  Google Scholar 

  • Loy F, Diana M, Isola R, Solinas P, Isola M, Conti G, Lantini MS, Cossu M, Riva A, Ekström J (2012) Morphological evidence that pentagastrin regulates secretion in the human parotid gland. J Anat 220:447–453

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Loy F, Isola M, Isola R, Lilliu MA, Solinas P, Conti G, Godoy T, Riva A, Ekström J (2013) The antipsychotic amisulpride: ultrastructural evidence of its secretory activity in salivary glands. Oral Dis 20:796–802

    PubMed  Google Scholar 

  • Loy F, Isola M, Isola R, Solinas P, Lilliu MA, Puxeddu R, Ekström J (2015) Ultrastructural evidence of a secretory role for melatonin in the human parotid gland. J Physiol Pharmacol 66:847–853

    Google Scholar 

  • Lu Y, Bennick A (1998) Interaction of tannin with human salivary proline-rich proteins. Arch Oral Biol 43:717–728

    Article  PubMed  CAS  Google Scholar 

  • Manconi B, Cabras T, Pisano E, Sanna MT, Olianas A, Fanos V, Faa G, Nemolato S, Iavarone F, Castagnola M, Messana I (2013) Modifications of the acidic soluble salivary proteome in human children from birth to the age of 48 months investigated by a top-down HPLC-ESI-MS platform. J Proteome 91:536–543

    Article  CAS  Google Scholar 

  • Manconi B, Cabras T, Sanna M, Piras V, Liori B, Pisano E, Iavarone F, Vincenzoni F, Cordaro M, Faa G, Castagnola M, Messana I (2016) N- and O-linked glycosylation site profiling of the human basic salivary proline-rich protein 3M. J Sep Sci 39:1987–1997

    Article  PubMed  CAS  Google Scholar 

  • Mandel SJ, Mandel L (2003) Radioactive iodine and the salivary glands. Thyroid 13:265–271

    Article  PubMed  CAS  Google Scholar 

  • Martin TJ, Conley SF (2007) Long-term efficacy of intra-oral surgery for sialorrhea. Otolaryngol Head Neck Surg 137:54–58

    Article  PubMed  Google Scholar 

  • Matsuo R (1999) Central connections for salivary innervations and efferent impulse formation. In: Garrett JR, Ekström J, Anderson LC (eds) Neural mechanisms of salivary gland secretion. Frontiers of oral biology, vol 11. Karger, Basel

    Google Scholar 

  • Melvin JE, Yule D, Shuttleworth T, Begenisich T (2005) Regulation of fluid and electrolyte secretion in salivary gland acinar cells. Annu Rev Physiol 67:445–469

    Article  PubMed  CAS  Google Scholar 

  • Messana I, Cabras T, Iavarone F, Manconi B, Huang L, Martelli C, Olianas A, Sanna MT, Pisano E, Sanna M, Arba M, D'Alessandro A, Desiderio C, Vitali A, Pirolli D, Tirone C, Lio A, Vento G, Romagnoli C, Cordaro M, Manni A, Gallenzi P, Fiorita A, Scarano E, Calò L, Passali GC, Picciotti PM, Paludetti G, Fanos V, Faa G, Castagnola M (2015) Chrono-proteomics of human saliva: variations of the salivary proteome during human development. J Proteome Res 14:1666–1677

    Article  PubMed  CAS  Google Scholar 

  • Messana I, Cabras T, Inzitari R, Lupi A, Zuppi C, Olmi C, Fadda MB, Cordaro M, Giardina B, Castagnola M (2004) Characterization of the human salivary basic proline-rich protein complex by a proteomic approach. J Proteome Res 3:792–800

    Article  PubMed  CAS  Google Scholar 

  • Messana I, Cabras T, Pisano E, Sanna MT, Olianas A, Manconi B, Pellegrini M, Paludetti G, Scarano E, Fiorita A, Agostino S, Contucci AM, Calò L, Picciotti PM, Manni A, Bennick A, Vitali A, Fanali C, Inzitari R, Castagnola M (2008a) Trafficking and postsecretory events responsible for the formation of secreted human salivary peptides: a proteomics approach. Mol Cell Proteomics 7:911–926

    Article  PubMed  CAS  Google Scholar 

  • Messana I, Inzitari R, Fanali C, Cabras T, Castagnola M (2008b) Facts and artifacts in proteomics of body fluids. What proteomics of saliva is telling us? J Sep Sci 31:1948–1963

    Article  PubMed  CAS  Google Scholar 

  • Mese H, Matsuo R (2007) Salivary secretion, taste and hyposalivation. Oral Rehabil 34:711–723

    Article  CAS  Google Scholar 

  • Meurman JH, Tarkkila L, Tiitinen A (2009) The menopause and oral health. Maturitas 63:56–62

    Article  PubMed  Google Scholar 

  • Nagler RM (2004) Salivary glands and the aging process: mechanistic aspects, health-status and medicinal-efficacy monitoring. Biogerontology 5:223–233

    Article  PubMed  CAS  Google Scholar 

  • Navazesh M, Kumar SKS (2008) Measuring salivary flow: challenges and opportunities. J Am Dent Assoc 139:35S–40S

    Article  PubMed  Google Scholar 

  • Nederfors T, Isaksson R, Mörnstad H, Dahlöf C (1997) Prevalence of perceived symptoms of dry mouth in an adult Swedish population – relation to age, sex and pharmacotherapy. Community Dent Oral Epidemiol 25:211–216

    Article  PubMed  CAS  Google Scholar 

  • Nederfors T, Twetman S, Dahlöf C (1989) Effects of the thiazide diuretic bendroflumethiazide on salivary flow rate and composition. Scand J Dent Res 97:520–527

    PubMed  CAS  Google Scholar 

  • Nemolato S, Messana I, Cabras T, Manconi B, Inzitari R, Fanali C, Vento G, Tirone C, Romagnoli C, Riva A, Fanni D, Di Felice E, Faa G, Castagnola M (2009) Thymosin beta(4) and beta(10) levels in pre-term newborn oral cavity and foetal salivary glands evidence a switch of secretion during foetal development. PLoS One 4:e5109

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Offner GD, Troxler RF (2000) Heterogeneity of high-molecular-weight human salivary mucins. Adv Dent Res 14:69–75

    Article  PubMed  CAS  Google Scholar 

  • Ohlin P (1966) Effects of isoprenaline treatment of secretory responses and respiratory enzymes of the submazillary gland of the rat. J Oral Ther Pharmacol 3:190–193

    PubMed  CAS  Google Scholar 

  • Ohshiro K, Rosenthal DI, Koomen JM, Streckfus CF, Chambers M, Kobayashi R, El-Naggar AK (2007) Pre-analytic saliva processing affect proteomic results and biomarker screening of head and neck squamous carcinoma. Int J Oncol 30:743–749

    PubMed  CAS  Google Scholar 

  • Ono K, Morimoto Y, Inoue H, Masuda W, Tanaka T, Inenaga K (2006) Relationship of the unstimulated whole saliva flow rate and salivary gland size estimated by magnetic resonance image in healthy young humans. Arch Oral Biol 51:345–349

    Article  PubMed  Google Scholar 

  • Oppenheim FG, Salih E, Siqueira WL, Zhang W, Helmerhorst EJ (2007) Salivary proteome and its genetic polymorphisms. Ann N Y Acad Sci 1098:22–50

    Article  PubMed  CAS  Google Scholar 

  • Österberg T, Landahl S, Heidegård B (1984) Salivary flow, saliva pH and buffering capacity in 70-yr-old men and women. J Oral Rehab 11:157–170

    Article  Google Scholar 

  • Österberg T, Birkhed D, Johanson CN, Svanborg A (1992) Longitudinal study of stimulated whole saliva in an elderly population. Scand J Dent Res 100:340–345

    PubMed  Google Scholar 

  • Oudhoff MJ, Bolscher JG, Nazmi K, Kalay H, van’t Hof W, Amerongen AV, Veerman EC (2008) Histatins are the major wound-closure stimulating factors in human saliva as identified in a cell culture assay. FASEB J 22:3805–3812

    Article  PubMed  CAS  Google Scholar 

  • Oudhoff MJ, Kroeze KL, Nazmi K, van den Keijbus PA, Vant Hof W, Fernandez-Borja M, Hordijk PL, Gibbs S, Bolscher JG, Veerman EC (2009a) Structure-activity analysis of histatin, a potent wound healing peptide from human saliva: cyclization of histatin potentiates molar activity 1,000-fold. FASEB J 23:3928–3935

    Article  PubMed  CAS  Google Scholar 

  • Oudhoff MJ, van den Keijbus PA, Kroeze KL, Nazmi K, Gibbs S, Bolscher JG, Veerman EC (2009b) Histatins enhance wound closure with oral and non-oral cells. J Dent Res 88:846–850

    Article  PubMed  CAS  Google Scholar 

  • Palmerini CA, Mazzoni M, Radicioni G, Marzano V, Granieri L, Iavarone F, Longhi R, Messana I, Cabras T, Sanna MT, Castagnola M, Vitali A (2016) Antagonistic effect of a salivary proline-rich peptide on the cytosolic Ca2+ mobilization induced by progesterone in oral squamous cancer cells. PLoS One 11:e0147925

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Peluso G, De Santis M, Inzitari R, Fanali C, Cabras T, Messana I, Castagnola M, Ferraccioli GF (2007) Proteomic study of salivary peptides and proteins in patients with Sjögren's syndrome before and after pilocarpine treatment. Arthritis Rheum 56:2216–2222

    Article  PubMed  CAS  Google Scholar 

  • Petracca M, Guidubaldi A, Ricciardi L, Ialongo T, Del Grande A, Mulas D, Di Stasio E, Bentivogli AR (2015) Botulinum toxin a and B in sialorrhea: long-term data and literature overview. Toxicon 107:129–140

    Article  PubMed  CAS  Google Scholar 

  • Phillips AC, Carroll D, Evans P, Bosch JA, Clow A, Hucklebridge F, Der D (2006) Stressful life events are associated with low secretion rates of immunoglobulin a in saliva in the middle aged and elderly. Bran Behav Immun 20:191–197

    Article  CAS  Google Scholar 

  • Pisano E, Cabras T, Montaldo C, Piras V, Inzitari R, Olmi C, Castagnola M, Messana I (2005) Peptides of human gingival crevicular fluid determined by HPLC-ESI-MS. Eur J Oral Sci 113:462–468

    Article  PubMed  CAS  Google Scholar 

  • Poulsen JH (1998) Secretion of electrolytes and water by salivary glands. In: Garrett JR, Ekström J, Anderson LC (eds) Glandular mechanisms of salivary secretion. Frontiers of oral biology, vol 10. Karger, Basel, pp 55–72

    Chapter  Google Scholar 

  • Praharaj SK, Jana AK, Goswami K, Das PR, Goyal N, Sinha VK (2010) Salivary flow rate in patients with schizophrenia on clozapine. Clin Neuropharmacol 33:176–178

    Article  PubMed  CAS  Google Scholar 

  • Radicioni G, Stringaro A, Molinari A, Nocca G, Longhi R, Pirolli D, Scarano E, Iavarone F, Manconi B, Cabras T, Messana I, Castagnola M, Vitali A (2015) Characterization of the cell penetrating properties of a human salivary proline-rich peptide. Biochim Biophys Acta 1848:2868–2877

    Article  PubMed  CAS  Google Scholar 

  • Ramachandran P, Boontheung P, Xie Y, Sondej M, Wong DT, Loo JA (2006) Identification of N-linked glycoproteins in human saliva by glycoprotein capture and mass spectrometry. J Proteome Res 5:1493–1503

    Article  PubMed  CAS  Google Scholar 

  • Reichert FL, Poth EJ (1933) Pathways for the secretory fibres of salivary glands in man. Proc Soc Exp Biol Med 30:973–977

    Article  Google Scholar 

  • Rho MB, Deschler DG (2005) Salivary gland anatomy. In: Witt RL (ed) Salivary gland diseases. Surgical and medical management. Thieme, New York Stuttgart

    Google Scholar 

  • Righino B, Pirolli D, Radicioni G, Marzano V, Longhi R, Arcovito A, Sanna MT, De Rosa MC, Paoluzi S, Cesareni G, Messana I, Castagnola M, Vitali A (2016) Structural studies and SH3 domain binding properties of a human antiviral salivary proline-rich peptide. Biopolymers 106:714–725

    Article  PubMed  CAS  Google Scholar 

  • Robinovitch MR, Ashley RL, Iversen JM, Vigoren EM, Oppenheim FG, Lamkin M (2001) Parotid salivary basic proline-rich proteins inhibit HIV-I infectivity. Oral Dis 7:86–93

    PubMed  CAS  Google Scholar 

  • Rossini RB, Machado AB, Machado CRS (1979) A histochemical study of catecholamines and cholinesterases in the autonomic nerves of human minor salivary glands. Histochem J 11:661–688

    Article  Google Scholar 

  • Ryan CM, Souda P, Halgand F, Wong DT, Loo JA, Faull KF, Whitelegge JP (2010) Confident assignment of intact mass tags to human salivary cystatins using top-down Fourier-transform ion cyclotron resonance mass spectrometry. J Am Soc Mass Spectrom 21:908–917

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ryu OH, Atkinson JC, Hoehn GT, Illei GG, Hart TC (2006) Identification of parotid salivary biomarkers in Sjogren's syndrome by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry and two-dimensional difference gel electrophoresis. Rheumatology (Oxford) 45:1077–1086

    Article  CAS  Google Scholar 

  • Sarosiek J, Rourk RM, Piascik R, Namiot Z, Hetzel DP, McCallum RW (1994) The effect of esophageal mechanical and chemical stimuli on salivary mucin secretion in healthy individuals. Am J Med Sci 308:23–31

    Article  PubMed  CAS  Google Scholar 

  • Sabatini LM, Carlock LR, Johnson GW, Azen EA (1987) cDNA cloning and chromosomal localization (4q11-13) of a gene for statherin, a regulator of calcium in saliva. Am J Hum Genet 41:1048–1060

    PubMed  PubMed Central  CAS  Google Scholar 

  • Sabatini LM, Azen EA (1989) Histatins, a family of salivary histidine-rich proteins, are encoded by at least two loci (HIS1 and HIS2). Biochem Biophys Res Commun 160:495–502

    Article  PubMed  CAS  Google Scholar 

  • Sayardoust S, Ekström J (2003) Nitric oxide-dependent in vitro secretion of amylase from innervated or chronically denervated parotid glands of the rat in response to isoprenaline and vasoactive intestinal peptide. Exp Physiol 88:381–387

    Article  PubMed  CAS  Google Scholar 

  • Sayardoust S, Ekström J (2004) Nitric oxide-dependent protein synthesis in parotid and submandibular glands of anaesthetized rats upon sympathetic stimulation or isoprenaline administration. Exp Physiol 89:219–227

    Article  PubMed  CAS  Google Scholar 

  • Scannapieco FA, Torres G, Levine MJ (1993) Salivary alpha-amylase: role in dental plaque and caries formation. Crit Rev Oral Biol Med 4:301–307

    Article  PubMed  CAS  Google Scholar 

  • Schafer CA, Schafer JJ, Yakob M, Lima P, Camargo P, Wong DT (2014) Saliva diagnostics: utilizing oral fluids to determine health status. Monogr Oral Sci 24:88–98

    Article  PubMed  Google Scholar 

  • Schon F (1985) Postsympathectomy pain and changes in sensory neuropeptides: towards an animal model. Lancet 2:1158–1160

    Article  PubMed  CAS  Google Scholar 

  • Schüpbach P, Oppenheim FG, Lendenmann U, Lamkin MS, Yao Y, Guggenheim B (2001) Electron-microscopic demonstration of proline-rich proteins, statherin, and histatins in acquired enamel pellicles in vitro. Eur J Oral Sci 109:60–68

    Article  PubMed  Google Scholar 

  • Schwartz SS, Hay DI, Schluckebier SK (1992) Inhibition of calcium phosphate precipitation by human salivary statherin: structure-activity relationships. Calcif Tissue Int 50:511–517

    Article  PubMed  CAS  Google Scholar 

  • Shafik A, El-Sibai O, Shafik AA, Mostafa R (2005) Effect of topical esophageal acidification on salivary secretion: identification of the mechanism of action. J Gastroenterol Hepatol 20:1935–1939

    Article  PubMed  Google Scholar 

  • Shapiro SL (1973) Recurrent parotid gland swelling. Eye Ear Nose Throat 52:147–150

    CAS  Google Scholar 

  • Shintani S, Hamakawa H, Ueyama Y, Hatori M, Toyoshima T (2010) Identification of a truncated cystatin SA-I as a saliva biomarker for oral squamous cell carcinoma using the SELDI ProteinChip platform. Int J Oral Maxillofac Surg 39:68–74

    Article  PubMed  CAS  Google Scholar 

  • Ship J, Pillemer SR, Baum BJ (2002) Xerostomia and the geriatric patient. J Am Geriatr Soc 50:535–543

    Article  PubMed  Google Scholar 

  • Siqueira WL, Salih E, Wan DL, Helmerhorst EJ, Oppenheim FG (2008) Proteome of human minor salivary gland secretion. J Dent Res 87:445–450

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sivadasan P, Gupta MK, Sathe GJ, Balakrishnan L, Palit P, Gowda H, Suresh A, Kuriakose MA, Sirdeshmukh R (2015) Human salivary proteome- a resource of potential biomarkers for oral cancer. Proteomics 127(Pt A):89–95

    Article  PubMed  CAS  Google Scholar 

  • Smaje LH (1998) Capillary dynamics in salivary glands. In: Garrett JR, Ekström J, Anderson LC (eds) Glandular mechanisms of salivary secretion. Frontiers of oral biology, vol 10. Karger, Basel

    Google Scholar 

  • Sockalingam S, Shammi C, Remington G (2007) Clozapine-induced hypersalivation: a review of treatment strategies. Can J Psychiatr 52:377–384

    Article  Google Scholar 

  • Steiner DF (1998) The proprotein convertases. Curr Opin Chem Biol 2:31–39

    Article  PubMed  CAS  Google Scholar 

  • Strous GJ, Dekker J (1992) Mucin-like glycoproteins. Crit Rev Biochem Mol Biol 27(5):7–92

    Google Scholar 

  • Tabak LA (2001) A revolution in biomedical assessment: the development of salivary diagnostics. J Dent Educ 65:1335–1339

    PubMed  CAS  Google Scholar 

  • Tandler B, Riva A (1986) Salivary glands. In: Mjör IA, Fejerskov O (eds) Human oral embryology and histology. Munksgaard, Copenhagen

    Google Scholar 

  • Teesalu S, Roosalu M (1993) Mixed salivary glucose and other carbohydrate leverls and their changes in emotional stress and in physical activity. Acta Physiol Scand 149:P57

    Google Scholar 

  • Tenouvo J (1998) Antimicrobial functions of human saliva – how important is it for oral health? Acta Odontol Scand 58:250–256

    Article  Google Scholar 

  • Thelin WR, Brennan MT, Lockhart PG, Singh ML, Foc PC, Papas AS, Boucher RC (2008) The oral mucosa as a therapeutic target for xerostomia. Oral Dis 14:683–689

    Article  PubMed  CAS  Google Scholar 

  • Thomsson KA, Prakobphol A, Leffler H, Reddy MS, Levine MJ, Fisher SJ, Hansson GC (2002) The salivary mucin MG1 (MUC5B) carries a repertoire of unique oligosaccharides that is large and diverse. Glycobiology 12:1–14

    Article  PubMed  CAS  Google Scholar 

  • Villa A, Wolff A, Narayana N, Dawes C, Aframian DJ, Lynge Pedersen AM, Vissink A, Aliko A, Sia YW, Joshi RK, McGowan R, Jensen SB, Kerr AR, Ekström J, Proctor G (2016) World Workshop on Oral Medicine VI: a systemic review of medication-induced salivary gland dysfunction. Oral Dis 22:365–382

    Google Scholar 

  • Vissink A, Spijkervet F, Amerongen A (1996) Aging and saliva: a review of the literature. Spec Care Dentist 16:95–103

    Article  PubMed  CAS  Google Scholar 

  • Wang Q, Yu Q, Lin Q, Duan Y (2015) Emerging salivary biomarkers by mass spectrometry. Clin Chim Acta 438:214–221

    Article  PubMed  CAS  Google Scholar 

  • Wärnberg GE, Einarson S, Jonsson M, Aronsson JI (2005) Impact of dry mouth on oral health-related quality of life in older people. Gerodontology 22:219–226

    Article  Google Scholar 

  • Wolff A, Joshi RK, Ekström J, Aframian D, Pedersen AML, Proctor G, Narayama N, Villa A, Sia YW, Aliko A, McGowan R, Kerr AR, Jensen SB, Vissink A, Dawes C (2017) A guide to medications inducing salivary gland dysfunction, xerostomia and subjective sialorrhea: a systematic review sponsored by the world workshop on oral medicine VI. Drugs R D 17:1–28

    Article  PubMed  CAS  Google Scholar 

  • Wolff MS, Kleinberg I (1999) The effect of ammonium glycopyrrolate (Robinul)-induced xerostomia on oral mucosal wetness and flow of gingival crevicular fluid in humans. Arch Oral Biol 44:97–102

    Article  PubMed  CAS  Google Scholar 

  • Wolff MS, Kleinberg I (1998) Oral mucosal wetness in hypo- and normosalivators. Arch Oral Biol 43:455–462

    Article  PubMed  CAS  Google Scholar 

  • Wu CC, Chu HW, Hsu CW, Chang KP, Liu HP (2015) Saliva proteome profiling reveals potential salivary biomarkers for detection of oral cavity squamous cell carcinoma. Proteomics 15:3394–3404

    Article  PubMed  CAS  Google Scholar 

  • Yao Y, Lamkin MS, Oppenheim FG (1999) Pellicle precursor proteins: acidic proline-rich proteins, statherin, and histatins, and their crosslinking reaction by oral transglutaminase. J Dent Res 78:1696–1703

    Article  PubMed  CAS  Google Scholar 

  • Young CA, Ellis C, Johnson J, Sathasivam S, Pih N (2011) Treatment for sialorrhea (excessive saliva) in people with motor neuron disease/amyotrophic lateral sclerosis. Cochrane Database Syst Rev 11(5):CD006981

    Google Scholar 

  • Zohar Y, Siegal A, Siegal G, Halpern M, Levy B, Gal R (2002) The great auricular nerve: does it penetrate the parotid gland? An anatomical and microscopical study. J Cranio-Maxillofac Surg 30:318–321

    Article  Google Scholar 

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Ekström, J., Khosravani, N., Castagnola, M., Messana, I. (2017). Saliva and the Control of Its Secretion. In: Ekberg, O. (eds) Dysphagia. Medical Radiology(). Springer, Cham. https://doi.org/10.1007/174_2017_143

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