SALIVA FORMATION STUDIED BY MICROPROBE ANALYSIS

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The long-term objectives are to understand several specific aspects of salivary gland function: (1) the mechanisms underlying salivary fluid production, (2) the mechanism underlying the exocytosis of secretory granules, and (3) the mechanisms which regulate the elemental composition of the nucleus. The specific aims are: (1) To use the electron microprobe technique to measure elemental concentrations of Na, Mg, P, S, Cl, K and Ca in cytoplasm, nuclei and secretory granules of resting and of cholinergically and adrenergically stimulated rat parotid gland acinar cells incubated in vitro. (2) To use the above findings to test the solute-solvent coupled hypothesis for salivary fluid production, i.e. to test whether intracellular osmolarity increases under conditions of salivary fluid production. (3) To use the above findings to test the hypothesis that a Ca-activated, osmotically driven passive process constitutes the mechanism underlying the exocytosis of secretory granules. (4) To use the above findings to test the hypothesis that the nuclear membrane is freely permeable to the diffusible ions, and that the nuclear elemental concentration changes are more sensitive to Beta-adrenergic agonists than to Alpha-adrenergic or cholinergic agonists. These findings will contribute to our understanding of the basic cellular processes of water transport across epithelial tissues, secretion of secretory granules by exocrine glands, and possibly mechanisms whereby signals can be presented to the nucleus in order to effect changes in nuclear metabolism, e.g. changes in RNA and DNA synthesis rates. These concepts may also contribute to our understanding of the salivary gland pathophysiology associated with cystic fibrosis, irradiation injury, graft-versus-host disease, and Sjogren's syndrome.