{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T03:59:51Z","timestamp":1771991991812,"version":"3.50.1"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,12,10]],"date-time":"2018-12-10T00:00:00Z","timestamp":1544400000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Anatomy"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Several beneficial effects on oral health are ascribed to melatonin. Due to its lipophilic nature, non\u2010protein\u2010bound circulating melatonin is usually thought to enter the saliva by passive diffusion through salivary acinar gland cells. Recently, however, using transmission electron microscopy (<jats:styled-content style=\"fixed-case\">TEM<\/jats:styled-content>), melatonin was found in acinar secretory granules of human salivary glands. To test the hypothesis that granular located melatonin is actively discharged into the saliva by exocytosis, i.e. contrary to the general belief, the \u03b2\u2010adrenergic receptor agonist isoprenaline, which causes the degranulation of acinar parotid serous cells, was administered to anaesthetised rats. Sixty minutes after an intravenous bolus injection of isoprenaline (5\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup>), the right parotid gland was removed; pre\u2010administration, the left control gland had been removed. Samples were processed to demonstrate melatonin reactivity using the immunogold staining method. Morphometric assessment was made using <jats:styled-content style=\"fixed-case\">TEM<\/jats:styled-content>. Gold particles labelling melatonin appeared to be preferentially associated with secretory granules, occurring in their matrix and at membrane level but, notably, it was also associated with vesicles, mitochondria and nuclei. Twenty\u2010six per cent of the total granular population (per 100\u00a0\u03bcm<jats:sup>2<\/jats:sup> per cell area) displayed melatonin labelling in the matrix; three\u2010quarters of this fraction disappeared (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) in response to isoprenaline, and melatonin reactivity appeared in dilated lumina. Thus, evidence is provided of an alternative route for melatonin to reach the gland lumen and the oral cavity by active release through exocytosis, a process which is under the influence of parasympathetic and sympathetic nervous activity and is the final event along the so\u2010called regulated secretory pathway. During its stay in granules, anti\u2010oxidant melatonin may protect their protein\/peptide constituents from damage.<\/jats:p>","DOI":"10.1111\/joa.12921","type":"journal-article","created":{"date-parts":[[2018,12,11]],"date-time":"2018-12-11T04:05:45Z","timestamp":1544501145000},"page":"338-345","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Melatonin release by exocytosis in the rat parotid gland"],"prefix":"10.1111","volume":"234","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6347-4682","authenticated-orcid":false,"given":"Michela","family":"Isola","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences Division of Cytomorphology University of Cagliari Cagliari 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