Localization of Zinc in the Rat Submandibular Gland and the Effect of its Deficiency on Salivary Secretion

Abstract

To clarify the role of zinc in the mechanism of salivary secretion, the effects of zinc deficiency on the morphologic findings and secretory function of the salivary gland were investigated with a rat model of chronic zinc deficiency, prepared by feeding a zinc-deficient diet, and a rat model of acute zinc deficiency, prepared by administration of a zinc chelator, dithizone. In rats with chronic zinc deficiency, the granule production in the granular duct cells was decreased, but the glandular epithelial cells and myoepithelial cells showed no degenerative or other destructive morphologic changes. The degranulation of the granular duct cells and acinar cells in response to acetylcholine hydrochloride seen in control rats was strongly inhibited in rats with acute and chronic zinc deficiency. The contractile response of the actin microfilament bundles in the myoepithelial cells to acetylcholine seen in the control rats was also absent in the zinc-deficient rats. Further, electron microscopy of the submandibular gland stained by Timm's method disclosed prominent zinc localization at the membrane surface, granules, and vesicles of the glandular epithelial cells and in the pits of the myoepithelial cells. These findings suggest that zinc, together with many zinc-dependent enzymes, is closely involved in the production and degranulation of secretory granules in the glandular epithelial cells, and also in the contraction of the myoepithelial cells in the submandibular gland.

The Zinc Sensing Receptor, ZnR/GPR39, in Health and Disease

“…Activation of ZnR/GPR39 was triggered by transient changes in extracellular Zn 2+ . While exogenous application of Zn 2+ may trigger ZnR/GPR39 activation, the endogenous sources of vesicular Zn 2+ may be the physiological trigger of ZnR/GPR39 activation, i.e., Zn 2+ released from neuronal vesicles, salivary gland vesicles, pancreatic enzymes, or Paneth cells in the intestinal epithelium [ 35 , 36 , 37 , 38 , 39 , 40 , 75 ]. In addition, extracellular Zn 2+ levels may transiently change following efflux mediated by Zn 2+ transporters, such as ZnT6 [ 76 ], or following injury and cell death [ 41 ].…”

“…Such vesicular Zn 2+ is found in neurons, epithelial Paneth cells of the intestine or the salivary gland, as well as in pancreatic β-cells [ 34 ]. The vesicular Zn 2+ can be released during normal activity of the cells; for example, Zn 2+ is released into the synapse during neuronal activity or is secreted from β-cells or mammary epithelial cells [ 35 , 36 , 37 , 38 , 39 , 40 ]. Release of Zn 2+ from cells can also occur following cellular injury and cell death, which liberates Zn 2+ from the numerous Zn 2+ -binding proteins or cellular organelles [ 41 ].…”

Overview of mammalian zinc transporters

“…This type of zinc is free or weakly bound and therefore detectable by several zinc-staining methods using its chelatable property. For example, chelatable zinc is found in the submandibular gland epithelial/myoepithelial cells [33], sperm cells [34,35] and pigment epithelial cells in the retina [36]. Moreover, more intimate analyses revealed chelatable zinc in subcellular compartments such as synaptic vesicles in telencephalic neurons [12,13], secretory granules in pancreatic b cells [14], pituitary secretory cells [37], submandibular gland granular convoluted tubule cells [38] and leukocytes [39], and apical secretory vesicles and lysosome-like structures in the epithelial cells of the lateral prostate [40].…”

The ZnR/GPR39 Interacts With the CaSR to Enhance Signaling in Prostate and Salivary Epithelia

“…Both prostate cancer and salivary ductal cells face physiologically relevant changes in extracellular Zn 2+ concentrations (Costello and Franklin, ; Wong et al, ; Iguchi et al, ; Gradinaru et al, ). In the salivary system Zn 2+ is packed in the secretory vesicles and is released by cholinergic activation while the seminal fluid contains the highest Zn 2+ concentration in the body (Frederickson et al, ; Ishii et al, ; Franklin et al, ; Huang et al, ). In both systems therefore, local changes in extracellular Zn 2+ may induce transient rises in extracellular Zn 2+ levels which will be removed by binding to serum proteins.…”