Subcellular distribution of melatonin receptors in human parotid glands

Abstract

The hormone melatonin influences oral health through a variety of actions, such as anti-inflammatory, antioxidant, immunomodulatory and antitumour. Many of these melatonin functions are mediated by a family of membrane receptors expressed in the oral epithelium and salivary glands. Using immunoblotting and immunohistochemistry, recent studies have shown that the melatonin membrane receptors, MT1 and MT2, are present in rat and human salivary glands. To date, no investigation has dealt with the ultrastructural distribution of the melatonin receptors. This was the aim of the present study, using the immunogold method applied to the human parotid gland. Reactivity to MT1 and, with less intensity, to MT2 appeared in the secretory granules of acinar cells and in the cytoplasmic vesicles of both acinar and ductal cells. Plasma membranes were also stained, albeit slightly. The peculiar intracytoplasmic distribution of these receptors may indicate that there is an uptake/transport system for melatonin from the circulation into the saliva.

Melatonin localization in human salivary glands

“…Melatonin receptors (MT1 and MT2) are transmembrane G protein‐coupled receptors whose activation triggers several intracellular signal cascades mediating cell responses such as salivary secretion . Although defined as membrane receptors, their presence in the cytoplasm also was recorded in human salivary gland cells, leading to propose that, beyond starting the signal cascades, they may be involved in melatonin transport within the cells . The melatonin localization shown here, quite identical to that recently described for receptors , strengthens the assumption that melatonin and receptors travel together into and throughout the cells.…”

“…Although defined as membrane receptors, their presence in the cytoplasm also was recorded in human salivary gland cells, leading to propose that, beyond starting the signal cascades, they may be involved in melatonin transport within the cells . The melatonin localization shown here, quite identical to that recently described for receptors , strengthens the assumption that melatonin and receptors travel together into and throughout the cells. In particular, the staining in basolateral cell membranes and nearby vesicles might indicate that circulating melatonin is captured by the membrane receptors and rapidly internalized.…”

“…The mechanism by which melatonin is accumulated in cell organelles should require the involvement of specific carriers, until now only hypothesized, which capture the hormone and allow its concentration in storage compartments . In our recent paper, melatonin receptors have been proposed for this role in salivary gland cells . Melatonin receptors (MT1 and MT2) are transmembrane G protein‐coupled receptors whose activation triggers several intracellular signal cascades mediating cell responses such as salivary secretion .…”

“…Thus, many questions about the source and transport of salivary melatonin still remain unanswered. In a recent paper , we have proposed that salivary glands, like other tissues , might have an intracellular machinery that facilitates melatonin uptake from blood, its transport through the cells and its storage. To confirm this hypothesis, it should be important to identify the specific cell compartments involved in the transport of melatonin as well as in its storage.…”

Diabetic Status Influences the Storage of Melatonin in Human Salivary Glands

“…Moreover, besides passive diffusion, new evidence supports the existence of an as yet not fully defined mechanism that may regulate the diffusion and storage of melatonin inside the cells (Venegas et al, ; Hevia et al, ). In our previous studies (Isola et al, ) carried out in human parotid glands, we suggested that melatonin receptors drive and store melatonin in secretory granules to be discharged into the lumen by granule exocytosis, which is elicited by a multitude of stimuli (Castle ; Castle and Castle, ). Hence, the level of salivary melatonin increases tremendously during actions that require enhanced salivation, such as chewing or speaking, i.e.…”