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Melatonin release by exocytosis in the rat parotid gland

Journal article
Authors M. Isola
Jörgen Ekström
R. Isola
F. Loy
Published in Journal of Anatomy
Volume 234
Issue 3
Pages 338-345
ISSN 0021-8782
Publication year 2019
Published at Institute of Neuroscience and Physiology, Department of Pharmacology
Pages 338-345
Language en
Keywords exocytosis, immunogold method, melatonin, parotid gland, secretion, transmission electron, subcellular-distribution, acinar degranulation, circadian-rhythm, secretion, transporters, pathways, receptor, proteins, amylase, Anatomy & Morphology
Subject categories Pharmacology and Toxicology


Several beneficial effects on oral health are ascribed to melatonin. Due to its lipophilic nature, non-protein-bound circulating melatonin is usually thought to enter the saliva by passive diffusion through salivary acinar gland cells. Recently, however, using transmission electron microscopy (TEM), 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 beta-adrenergic 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 mg kg(-1)), the right parotid gland was removed; pre-administration, the left control gland had been removed. Samples were processed to demonstrate melatonin reactivity using the immunogold staining method. Morphometric assessment was made using TEM. 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-six per cent of the total granular population (per 100 mu m(2) per cell area) displayed melatonin labelling in the matrix; three-quarters of this fraction disappeared (P < 0.01) 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-called regulated secretory pathway. During its stay in granules, anti-oxidant melatonin may protect their protein/peptide constituents from damage.

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