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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
2R01DE006373-04
Application #
3219958
Study Section
Oral Biology and Medicine Study Section (OBM)
Project Start
1983-03-01
Project End
1989-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
4
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
Schools of Dentistry/Oral Hygn
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Izutsu, K T; Cantino, M E; Johnson, D E (1994) A review of electron probe X-ray microanalysis studies of salivary gland cells. Microsc Res Tech 27:71-9
Wong, J G; Izutsu, K T; Robinovitch, M R et al. (1991) Microprobe analysis of maturation-related elemental changes in rat parotid secretory granules. Am J Physiol 261:C1033-41
Izutsu, K; Wilkinson, L; Oda, D et al. (1991) Comparison of elemental concentrations in the acinar cells of the human labial salivary gland. Arch Oral Biol 36:727-35
Allan, B J; Izutsu, K T; Ramsey, B W et al. (1990) Cyclic nucleotide responses in control and cystic fibrosis labial glands. Am J Physiol 258:R1320-6
Izutsu, K T; Ensign, W Y; Ramsey, B W et al. (1989) Potassium release in labial glands from controls and patients with cystic fibrosis. Lab Invest 60:158-60
Goddard, M K; Izutsu, K T; Johnson, D E et al. (1988) Evidence for two conductance/exchange pathways for chloride in rat parotid secretory granules. Biochem Biophys Res Commun 155:984-9
Johnson, D; Izutsu, K; Cantino, M et al. (1988) High spatial resolution spectroscopy in the elemental microanalysis and imaging of biological systems. Ultramicroscopy 24:221-35
Izutsu, K T; Schubert, M M; Truelove, E L et al. (1987) Use of human minor salivary glands in basic and applied secretion research. J Dent Res 66 Spec No:654-9
Izutsu, K T; Johnson, D E; Goddard, M (1987) Intracellular elemental concentrations in resting and secreting rat parotid glands. J Dent Res 66:537-40
Izutsu, K T; Johnson, D E (1986) Changes in elemental concentrations of rat parotid acinar cells following pilocarpine stimulation. J Physiol 381:297-309

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