{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T19:57:54Z","timestamp":1772567874501,"version":"3.50.1"},"reference-count":55,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"vor","delay-in-days":12,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100013003","name":"Universit\u00e0 degli Studi di Cagliari","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100013003","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Tissue Res"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Nitric oxide plays a crucial role in multiple physiological processes in salivary glands, yet its precise cellular sources in human glandular tissues remain insufficiently characterized. This study investigated the distribution and subcellular localization of neuronal nitric oxide synthase (nNOS) in human parotid and submandibular gland tissue samples obtained from surgical biopsies and autopsies, using both light and electron-microscope immunohistochemistry. In both gland types, nNOS was consistently observed in serous secretory cells and the ductal epithelium, whereas mucous cells showed no immunoreactivity. Ductal cell staining was heterogeneous, with some cells displaying intense labeling and others remaining unstained. Nerve fibers containing the enzyme were rare within the gland parenchyma. Ultrastructural analysis revealed the enzyme within secretory granules and small cytoplasmic vesicles of serous cells, as well as in the apical and basal cytoplasm, mitochondria, and nuclei of ductal epithelial cells. These findings provide the first ultrastructural evidence of nNOS in secretory and ductal cells of human major salivary glands. The selective localization in serous cells, absence in mucous cells, and limited nitrergic innervation suggest a substantial parenchymal contribution to nitric oxide production. This distribution indicates that nitric oxide regulates saliva formation, composition, and intracellular signaling and could play a broader role in oral physiology and disease.<\/jats:p>","DOI":"10.1007\/s00441-026-04048-7","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T04:10:57Z","timestamp":1770955857000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuronal nitric oxide synthase expression in secretory cells of the human parotid and submandibular salivary glands: evidence from light and electron microscopy"],"prefix":"10.1007","volume":"403","author":[{"given":"Michela","family":"Isola","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianna","family":"Boi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Demontis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raffaella","family":"Isola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Loy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Maxia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Murtas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Pina","family":"Serra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00f6rgen","family":"Ekstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Quartu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,2,13]]},"reference":[{"key":"4048_CR1","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1007\/BF02388306","volume":"27","author":"P Alm","year":"1995","unstructured":"Alm P, Uvelius B, Ekstr\u00f6m J, Holmqvist B, Larsson B, Andersson KE (1995) Nitric oxide synthase-containing neurons in rat parasympathetic, sympathetic and sensory ganglia: a comparative study. Histochem J 27:819\u2013831","journal-title":"Histochem J"},{"key":"4048_CR2","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1023\/a:1026452715555","volume":"29","author":"P Alm","year":"1997","unstructured":"Alm P, Ekstr\u00f6m J, Larsson B, Tobin G, Andersson KE (1997) Nitric oxide synthase immunoreactive nerves in rat and ferret salivary glands, and effects of denervation. Histochem J 29:669\u2013676. https:\/\/doi.org\/10.1023\/a:1026452715555","journal-title":"Histochem J"},{"key":"4048_CR3","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.jdsr.2015.08.001","volume":"52","author":"K Ambe","year":"2016","unstructured":"Ambe K, Watanabe H, Takahashi S, Nakagawa T, Sasaki J (2016) Production and physiological role of NO in the oral cavity. Jpn Dent Sci Rev 52:14\u201321. https:\/\/doi.org\/10.1016\/j.jdsr.2015.08.001","journal-title":"Jpn Dent Sci Rev"},{"key":"4048_CR4","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1074\/jbc.M113.506733","volume":"289","author":"K Aquilano","year":"2014","unstructured":"Aquilano K, Baldelli S, Ciriolo MR (2014) Nuclear recruitment of neuronal nitric-oxide synthase by \u03b1-syntrophin is crucial for the induction of mitochondrial biogenesis. J Biol Chem 289:365\u2013378. https:\/\/doi.org\/10.1074\/jbc.M113.506733","journal-title":"J Biol Chem"},{"key":"4048_CR5","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1111\/j.1600-079X.2008.00609.x","volume":"45","author":"HC Aras","year":"2008","unstructured":"Aras HC, Ekstr\u00f6m J (2008) Melatonin-evoked in vivo secretion of protein and amylase from the parotid gland of the anaesthetised rat. J Pineal Res 45:413\u2013421. https:\/\/doi.org\/10.1111\/j.1600-079X.2008.00609.x","journal-title":"J Pineal Res"},{"key":"4048_CR6","doi-asserted-by":"publisher","first-page":"36","DOI":"10.5115\/acb.2015.48.1.36","volume":"48","author":"S Asakawa","year":"2015","unstructured":"Asakawa S, Yamamoto M, Katori Y, Murakami G, Kasahara M, Matsunaga S, Abe S (2015) Innervation of submandibular and sublingual glands in elderly donated cadavers. Anat Cell Biol 48:36\u201343. https:\/\/doi.org\/10.5115\/acb.2015.48.1.36","journal-title":"Anat Cell Biol"},{"key":"4048_CR7","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1006\/bbrc.1993.1826","volume":"194","author":"S Bodis","year":"1993","unstructured":"Bodis S, Haregewoin A (1993) Evidence for the release and possible neural regulation of nitric oxide in human saliva. Biochem Biophys Res Commun 194:347\u2013350. https:\/\/doi.org\/10.1006\/bbrc.1993.1826","journal-title":"Biochem Biophys Res Commun"},{"key":"4048_CR8","doi-asserted-by":"publisher","DOI":"10.1016\/j.aanat.2024.152291","volume":"255","author":"M Boi","year":"2024","unstructured":"Boi M, Demontis R, Isola M, Isola R, Loy F, Serra MP, Trucas M, Ekstr\u00f6m J, Quartu M (2024) The human major sublingual gland and its neuropeptidergic and nitrergic innervations. Ann Anat 255:152291. https:\/\/doi.org\/10.1016\/j.aanat.2024.152291","journal-title":"Ann Anat"},{"key":"4048_CR9","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/S0014-2999(00)00918-3","volume":"411","author":"D Bredenb\u00f6ker","year":"2001","unstructured":"Bredenb\u00f6ker D, Dyarmand D, Meingast U, Fehmann HC, Staats P, Von Wichert P, Wagner U (2001) Effects of the nitric oxide\/cGMP system compared with the cAMP system on airway mucus secretion in the rat. Eur J Pharmacol 411:319\u2013325. https:\/\/doi.org\/10.1016\/S0014-2999(00)00918-3","journal-title":"Eur J Pharmacol"},{"key":"4048_CR10","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1016\/s0092-8674(00)81053-3","volume":"84","author":"JE Brenman","year":"1996","unstructured":"Brenman JE, Chao DS, Gee SH, McGee AW, Craven SE, Santillano DR, Wu Z, Huang F, Xia H, Peters MF, Froehner SC, Bredt DS (1996) Interaction of nitric oxide synthase with PSD-95 and \u03b11-syntrophin mediated by PDZ domains. Cell 84:757\u2013767. https:\/\/doi.org\/10.1016\/s0092-8674(00)81053-3","journal-title":"Cell"},{"key":"4048_CR11","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/s0003-9969(02)00183-8","volume":"48","author":"PA Brennan","year":"2003","unstructured":"Brennan PA, Thomas GJ, Langdon JD (2003) The role of nitric oxide in oral diseases. Arch Oral Biol 48:93\u2013100. https:\/\/doi.org\/10.1016\/s0003-9969(02)00183-8","journal-title":"Arch Oral Biol"},{"key":"4048_CR12","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/0014-2999(92)90824-n","volume":"223","author":"JF Brown","year":"1992","unstructured":"Brown JF, Hanson PJ, Whittle BJ (1992) Nitric oxide donors increase mucus gel thickness in rat stomach. Eur J Pharmacol 223:103\u2013104. https:\/\/doi.org\/10.1016\/0014-2999(92)90824-n","journal-title":"Eur J Pharmacol"},{"key":"4048_CR13","doi-asserted-by":"publisher","first-page":"G418","DOI":"10.1152\/ajpgi.1993.265.3.G418","volume":"265","author":"JF Brown","year":"1993","unstructured":"Brown JF, Keates AC, Hanson PJ, Whittle BJ (1993) Nitric oxide generators and cGMP stimulate mucus secretion by rat gastric mucosal cells. Am J Physiol 265:G418-422. https:\/\/doi.org\/10.1152\/ajpgi.1993.265.3.G418","journal-title":"Am J Physiol"},{"key":"4048_CR14","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1113\/expphysiol.2006.033639","volume":"91","author":"H Cevik Aras","year":"2006","unstructured":"Cevik Aras H, Ekstr\u00f6m J (2006) Pentagastrin-induced protein synthesis in the parotid gland of the anaesthetized rat, and its dependence on CCK-A and -B receptors and nitric oxide generation. Exp Physiol 91:673\u2013679. https:\/\/doi.org\/10.1113\/expphysiol.2006.033639","journal-title":"Exp Physiol"},{"key":"4048_CR15","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1111\/j.1600-079X.2008.00609.x","volume":"45","author":"H \u00c7evik-Aras","year":"2008","unstructured":"\u00c7evik-Aras H, Ekstr\u00f6m J (2008) Melatonin-evoked secretion of protein and amylase from the parotid gland of the anaesthetized rat. J Pineal Res 45:413\u2013421. https:\/\/doi.org\/10.1111\/j.1600-079X.2008.00609.x","journal-title":"J Pineal Res"},{"key":"4048_CR16","first-page":"95","volume":"62","author":"H \u00c7evik-Aras","year":"2011","unstructured":"\u00c7evik-Aras H, Godoy T, Ekstr\u00f6m J (2011) Melatonin-induced protein synthesis in the rat parotid gland. J Physiol Pharmacol 62:95\u201399","journal-title":"J Physiol Pharmacol"},{"key":"4048_CR17","doi-asserted-by":"publisher","first-page":"3024","DOI":"10.1038\/sj.emboj.7601207","volume":"25","author":"M Chvanov","year":"2006","unstructured":"Chvanov M, Gerasimenko OV, Petersen OH, Tepikin AV (2006) Calcium-dependent release of NO from intracellular S-nitrosothiols. EMBO J 25:3024\u20133032. https:\/\/doi.org\/10.1038\/sj.emboj.7601207","journal-title":"EMBO J"},{"key":"4048_CR18","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1159\/000061091","volume-title":"Glandular Mechanisms of Salivary Secretion","author":"AV Edwards","year":"1998","unstructured":"Edwards AV (1998) Autonomic control of salivary blood flow. In: Garrett JR, Ekstr\u00f6m J, Anderson LC (eds) Glandular Mechanisms of Salivary Secretion. Karger, Basel, pp 101\u2013117. https:\/\/doi.org\/10.1159\/000061091"},{"key":"4048_CR19","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1016\/j.archoralbio.2004.04.007","volume":"49","author":"J Ekstr\u00f6m","year":"2004","unstructured":"Ekstr\u00f6m J, Sayardoust S, Cevik H (2004) Nitric oxide-dependent mitotic activity in salivary glands of the rat upon sympathetic stimulation. Arch Oral Biol 49:889\u2013894. https:\/\/doi.org\/10.1016\/j.archoralbio.2004.04.007","journal-title":"Arch Oral Biol"},{"key":"4048_CR20","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/S1349-0079(07)80013-2","volume":"49","author":"J Ekstr\u00f6m","year":"2007","unstructured":"Ekstr\u00f6m J, Aras H\u00c7, 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\u201338. https:\/\/doi.org\/10.1016\/S1349-0079(07)80013-2","journal-title":"J Oral Biosci"},{"key":"4048_CR21","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1177\/2380084419834236","volume":"4","author":"S Fernando","year":"2019","unstructured":"Fernando S, Tadakamadla SK, Bakr M, Scuffham PA, Johnson NW (2019) Indicators of risk for dental caries in children. JDR Clin Trans Res 4:333\u2013341. https:\/\/doi.org\/10.1177\/2380084419834236","journal-title":"JDR Clin Trans Res"},{"key":"4048_CR22","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1177\/002215540004800808","volume":"48","author":"M Garc\u00eda-Vitoria","year":"2000","unstructured":"Garc\u00eda-Vitoria M, Garc\u00eda-Corch\u00f3n C, Rodr\u00edguez JA, Garc\u00eda-Amigot F, Burrell MA (2000) Expression of neuronal nitric oxide synthase in several cell types of the rat gastric epithelium. J Histochem Cytochem 48:1111\u20131120. https:\/\/doi.org\/10.1177\/002215540004800808","journal-title":"J Histochem Cytochem"},{"key":"4048_CR23","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/j.tips.2005.02.005","volume":"26","author":"P Ghafourifar","year":"2005","unstructured":"Ghafourifar P, Cadenas E (2005) Mitochondrial nitric oxide synthase. Trends Pharmacol Sci 26:190\u2013195. https:\/\/doi.org\/10.1016\/j.tips.2005.02.005","journal-title":"Trends Pharmacol Sci"},{"key":"4048_CR24","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1007\/BF01011504","volume":"6","author":"JD Harrison","year":"1974","unstructured":"Harrison JD (1974) Minor salivary glands of man: enzyme and mucosubstance histochemical studies. Histochem J 6:633\u2013647. https:\/\/doi.org\/10.1007\/BF01011504","journal-title":"Histochem J"},{"key":"4048_CR25","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1002\/cm.21520","volume":"76","author":"AL Horenberg","year":"2019","unstructured":"Horenberg AL, Houghton AM, Pandey S, Seshadri V, Guilford WH (2019) S-nitrosylation of cytoskeletal proteins. Cytoskeleton 76:243\u2013253. https:\/\/doi.org\/10.1002\/cm.21520","journal-title":"Cytoskeleton"},{"key":"4048_CR26","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1111\/joa.13996","volume":"244","author":"M Isola","year":"2024","unstructured":"Isola M, Maxia C, Murtas D, Ekstr\u00f6m J, Isola R, Loy F (2024) Prostate-specific antigen in the human salivary glands. J Anat 244:873\u2013881. https:\/\/doi.org\/10.1111\/joa.13996","journal-title":"J Anat"},{"key":"4048_CR27","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1016\/j.micron.2008.10.007","volume":"40","author":"AC Issy","year":"2009","unstructured":"Issy AC, da Silva CA, Guimar\u00e3es FS, Del Bel EA (2009) Effects of isoproterenol and NOS inhibitors on rat salivary ducts. Micron 40:343\u2013349. https:\/\/doi.org\/10.1016\/j.micron.2008.10.007","journal-title":"Micron"},{"key":"4048_CR28","first-page":"284","volume":"26","author":"JC Jeong","year":"2000","unstructured":"Jeong JC, Kim SH, Ryu SY (2000) Distribution of nitric oxide synthase isoforms in perioral exocrine glands in rats. J Korean Assoc Oral Maxillofac Surg 26:284\u2013292","journal-title":"J Korean Assoc Oral Maxillofac Surg"},{"key":"4048_CR29","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1002\/art.1780400515","volume":"40","author":"YT Konttinen","year":"1997","unstructured":"Konttinen YT, Platts LA, Tuominen S, Eklund KK, Santavirta N, T\u00f6rnwall J, Sorsa T, Hukkanen M, Polak JM (1997) Role of nitric oxide in Sj\u00f6gren\u2019s syndrome. Arthritis Rheum 40:875\u2013883. https:\/\/doi.org\/10.1002\/art.1780400515","journal-title":"Arthritis Rheum"},{"key":"4048_CR30","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/0304-3940(95)11594-M","volume":"192","author":"Z Lohinai","year":"1995","unstructured":"Lohinai Z, Sz\u00e9kely AD, So\u00f3s L, Feh\u00e9r E (1995) Elements containing nitric oxide synthase in feline submandibular gland. Neurosci Lett 192:9\u201312. https:\/\/doi.org\/10.1016\/0304-3940(95)11594-M","journal-title":"Neurosci Lett"},{"key":"4048_CR31","doi-asserted-by":"publisher","unstructured":"Lohinai Z, Burghardt B, Zelles T, Varga G (1997) The effect of L-arginine\/nitric oxide pathway on salivary amylase secretion in conscious rats. J Physiol Paris 91:217-221. https:\/\/doi.org\/10.1016\/s0928-4257(97)89488-0","DOI":"10.1016\/s0928-4257(97)89488-0"},{"key":"4048_CR32","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1159\/000026342","volume":"5","author":"A Lomniczi","year":"1998","unstructured":"Lomniczi A, Suburo AM, Elverdin JC, Mastronardi CA, Diaz S, Rettori V, McCann SM (1998) Role of nitric oxide in salivary secretion. NeuroImmunoModulation 5:226\u2013233. https:\/\/doi.org\/10.1159\/000026342","journal-title":"NeuroImmunoModulation"},{"key":"4048_CR33","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1177\/08959374000140011001","volume":"14","author":"DK Looms","year":"2000","unstructured":"Looms DK, Dissing S, Tritsaris K, Pedersen AM, Nauntofte B (2000) Adrenoceptor-activated nitric oxide synthesis in salivary acinar cells. Adv Dent Res 14:62\u201368. https:\/\/doi.org\/10.1177\/08959374000140011001","journal-title":"Adv Dent Res"},{"key":"4048_CR34","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1034\/j.1600-0714.2002.00047.x","volume":"31","author":"D Looms","year":"2002","unstructured":"Looms D, Tritsaris K, Pedersen AM, Nauntofte B, Dissing S (2002) Nitric oxide signalling in salivary glands. J Oral Pathol Med 31:569\u2013584. https:\/\/doi.org\/10.1034\/j.1600-0714.2002.00047.x","journal-title":"J Oral Pathol Med"},{"key":"4048_CR35","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2019.104571","volume":"109","author":"F Loy","year":"2020","unstructured":"Loy F, Serra MP, Boi M, Isola R, Ekstr\u00f6m J, Quartu M (2020) Catecholaminergic and cholinergic fibres in the human major sublingual gland. Arch Oral Biol 109:104571. https:\/\/doi.org\/10.1016\/j.archoralbio.2019.104571","journal-title":"Arch Oral Biol"},{"key":"4048_CR36","first-page":"1","volume":"622","author":"A Modin","year":"1994","unstructured":"Modin A (1994) Non-adrenergic, non-cholinergic vascular control with reference to neuropeptide Y, VIP and nitric oxide. Acta Physiol Scand Suppl 622:1\u201374.","journal-title":"Acta Physiol Scand Suppl"},{"key":"4048_CR37","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1177\/014107689909200402","volume":"92","author":"S Moncada","year":"1999","unstructured":"Moncada S (1999) Nitric oxide: discovery and impact on clinical medicine. J R Soc Med 92:164\u2013169. https:\/\/doi.org\/10.1177\/014107689909200402","journal-title":"J R Soc Med"},{"key":"4048_CR38","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/0034-5687(95)00042-C","volume":"102","author":"M Nagaki","year":"1995","unstructured":"Nagaki M, Shimura MN, Irokawa T, Sasaki T, Shirato K (1995) Nitric oxide regulation of glycoconjugate secretion from airways. Respir Physiol 102:89\u201395. https:\/\/doi.org\/10.1016\/0034-5687(95)00042-C","journal-title":"Respir Physiol"},{"key":"4048_CR39","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1111\/joor.12664","volume":"45","author":"AML Pedersen","year":"2018","unstructured":"Pedersen AML, S\u00f8rensen CE, Proctor GB, Carpenter GH, Ekstr\u00f6m J (2018) Salivary secretion in health and disease. J Oral Rehabil 45:730\u2013746. https:\/\/doi.org\/10.1111\/joor.12664","journal-title":"J Oral Rehabil"},{"key":"4048_CR40","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1172\/JCI40736","volume":"120","author":"JM Percival","year":"2010","unstructured":"Percival JM, Anderson KN, Huang P, Adams ME, Froehner SC (2010) Golgi and sarcolemmal nNOS regulate fatigue and vasoconstriction in exercising muscle. J Clin Invest 120:816\u2013826. https:\/\/doi.org\/10.1172\/JCI40736","journal-title":"J Clin Invest"},{"key":"4048_CR41","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1111\/j.1476-5381.1996.tb15498.x","volume":"118","author":"SI Ramnarine","year":"1996","unstructured":"Ramnarine SI, Khawaja AM, Barnes PJ, Rogers DF (1996) Nitric oxide inhibition of basal and neurogenic mucus secretion. Br J Pharmacol 118:998\u20131002. https:\/\/doi.org\/10.1111\/j.1476-5381.1996.tb15498.x","journal-title":"Br J Pharmacol"},{"key":"4048_CR42","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/s0014-2999(02)01375-4","volume":"439","author":"F Rosignoli","year":"2002","unstructured":"Rosignoli F, P\u00e9rez Leir\u00f3s C (2002) Muscarinic activation of nitric oxide synthase in rat parotid gland. Eur J Pharmacol 439:27\u201333. https:\/\/doi.org\/10.1016\/s0014-2999(02)01375-4","journal-title":"Eur J Pharmacol"},{"key":"4048_CR43","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1113\/eph8802543","volume":"88","author":"S Sayardoust","year":"2003","unstructured":"Sayardoust S, Ekstr\u00f6m 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\u2013387. https:\/\/doi.org\/10.1113\/eph8802543","journal-title":"Exp Physiol"},{"key":"4048_CR44","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1113\/expphysiol.2003.002648","volume":"89","author":"S Sayardoust","year":"2004","unstructured":"Sayardoust S, Ekstr\u00f6m 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\u2013227. https:\/\/doi.org\/10.1113\/expphysiol.2003.002648","journal-title":"Exp Physiol"},{"key":"4048_CR45","doi-asserted-by":"publisher","first-page":"374","DOI":"10.18805\/ijar.10714","volume":"50","author":"AD Singh","year":"2016","unstructured":"Singh AD, Singh O (2016) Histoenzymic studies on sublingual salivary gland of buffalo during prenatal development. Indian J Anim Res 50:374\u2013376. https:\/\/doi.org\/10.18805\/ijar.10714","journal-title":"Indian J Anim Res"},{"key":"4048_CR46","doi-asserted-by":"publisher","first-page":"745","DOI":"10.3390\/jcm9030745","volume":"9","author":"A Skutnik-Radziszewska","year":"2020","unstructured":"Skutnik-Radziszewska A, Maciejczyk M, Flisiak I, Ko\u0142odziej JKU, Kotowska-Rodziewicz A, Klimiuk A, Zalewska A (2020) Inflammation and nitrosative stress in saliva and plasma in psoriasis. J Clin Med 9:745. https:\/\/doi.org\/10.3390\/jcm9030745","journal-title":"J Clin Med"},{"key":"4048_CR47","first-page":"325","volume":"53","author":"BL Slomiany","year":"2002","unstructured":"Slomiany BL, Slomiany A (2002) Nitric oxide interferes with salivary mucin synthesis: involvement of ERK and p38 mitogen-activated protein kinase. J Physiol Pharmacol 53:325\u2013336","journal-title":"J Physiol Pharmacol"},{"key":"4048_CR48","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1002\/(SICI)1097-0029(19960901)35:1<32::AID-JEMT4>3.0.CO;2-U","volume":"35","author":"S Soinila","year":"1996","unstructured":"Soinila S, Vanhatalo S, Lumme A, B\u0103ck N, Soinila J (1996) Nitric oxide synthase in the autonomic and sensory ganglia innervating the submandibular salivary gland. Microsc Res Tech 35:32\u201343. https:\/\/doi.org\/10.1002\/(SICI)1097-0029(19960901)35:1%3c32::AID-JEMT4%3e3.0.CO;2-U","journal-title":"Microsc Res Tech"},{"key":"4048_CR49","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1007\/s00418-005-0123-8","volume":"125","author":"J Soinila","year":"2006","unstructured":"Soinila J, Nuorva K, Soinila S (2006) Nitric oxide synthase in human salivary glands. Histochem Cell Biol 125:717\u2013723. https:\/\/doi.org\/10.1007\/s00418-005-0123-8","journal-title":"Histochem Cell Biol"},{"key":"4048_CR50","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1902\/jop.2016.150639","volume":"87","author":"CR Stewart","year":"2016","unstructured":"Stewart CR, Obi N, Epane EC, Akbari AA, Halpern L, Southerland JH, Gangula PR (2016) Diabetes effects on salivary BH4 and nitric oxide synthesis. J Periodontol 87:735\u2013741. https:\/\/doi.org\/10.1902\/jop.2016.150639","journal-title":"J Periodontol"},{"key":"4048_CR51","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1054\/ceca.2001.0218","volume":"30","author":"H Sugiya","year":"2001","unstructured":"Sugiya H, Mitsui Y, Michikawa H, Fujita-Yoshigaki J, Hara-Yokoyama M, Hashimoto S, Furuyama S (2001) Ca(2+)-regulated nitric oxide generation in rabbit parotid acinar cells. Cell Calcium 30:107\u2013116. https:\/\/doi.org\/10.1054\/ceca.2001.0218","journal-title":"Cell Calcium"},{"key":"4048_CR52","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1016\/s0003-9969(99)00064-3","volume":"44","author":"N Takai","year":"1999","unstructured":"Takai N, Uchihashi K, Higuchi K, Yoshida Y, Yamaguchi M (1999) Localization of neuronal NOS and regulation of secretion in rat salivary glands. Arch Oral Biol 44:745\u2013750. https:\/\/doi.org\/10.1016\/s0003-9969(99)00064-3","journal-title":"Arch Oral Biol"},{"key":"4048_CR53","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1016\/j.bbabio.2017.02.009","volume":"1858","author":"CH Tengan","year":"2017","unstructured":"Tengan CH, Moraes CT (2017) NO control of mitochondrial function in normal and transformed cells. Biochim Biophys Acta Bioenerg 1858:573\u2013581. https:\/\/doi.org\/10.1016\/j.bbabio.2017.02.009","journal-title":"Biochim Biophys Acta Bioenerg"},{"key":"4048_CR54","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1113\/expphysiol.1997.sp004067","volume":"82","author":"G Tobin","year":"1997","unstructured":"Tobin G, Edwards AV, Bloom SR, Ekstr\u00f6m J (1997) Nitric oxide in control of submandibular gland function in the anaesthetized\u00a0ferret. Exp Physiol 82:825\u2013836. https:\/\/doi.org\/10.1113\/expphysiol.1997.sp004067","journal-title":"Exp Physiol"},{"key":"4048_CR55","doi-asserted-by":"publisher","unstructured":"Zhang HQ, Fast W, Marletta MA, Martasek P, Silverman RB (1997) Selective inhibition of neuronal NOS by n\u03c9-propyl-l-arginine. J Med Chem 40:3869\u20133870. https:\/\/doi.org\/10.1021\/jm970550g","DOI":"10.1021\/jm970550g"}],"container-title":["Cell and Tissue Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00441-026-04048-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00441-026-04048-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00441-026-04048-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T19:02:35Z","timestamp":1772564555000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00441-026-04048-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":55,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["4048"],"URL":"https:\/\/doi.org\/10.1007\/s00441-026-04048-7","relation":{},"ISSN":["0302-766X","1432-0878"],"issn-type":[{"value":"0302-766X","type":"print"},{"value":"1432-0878","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"14 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was approved by the Independent Ethics Committee (IEC) of the Azienda Ospedaliero-Universitaria of Cagliari, Italy (Prot. PG\/2019\/10454 \u2013 Part 2.1).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"19"}}