The principal object of this project is to extend our studies on the effect of Ca2+ mobilizing hormones on the Ca2+ permeability and Ca2+ pump of the intracellular stores of pancreatic acinar cells. This constitutes as essential stage towards understanding the mechanisms of release and reloading of the intracellular stores with Ca2+upton cell stimulation and removal of stimuli. To date, we have developed techniques; to measure free cytosolic Ca2+ in intact pancreatic acinar cells using the Ca2+ sensitive dye FURA 2; to specifically label the hormone mobilizable intracellular pool with 45Ca in intact cells; to measure Ca2+ channel mediated - 45Ca fluxes in intact and permeabilized cells; and to measure Ca2+ pump mediated -45Ca fluxes in permeabilized cells. Using these techniques, the immediate aims are (a) demonstration that Ca2+ release from the intracellular pool is sufficient to activate the plasma membrane Ca2+ channel. Activation of this channel is not directly mediated and does not require the presence of the hormone. (b) Show that the hormone, like IP3, activates a Ca2+ channel in the endoplasmic reticulum membrane. (c) Compare the effects of IP3, GTP and arachidonic acid with the hormone activated Ca2+ release from the intracellular pool. (d) Study the contribution of IP3, GTP and arachidonic acid to the hormone dependent Ca2+ release (e) define the requirements for the newly discovered, activation of the endoplasmic reticulum Ca2+ pump by the Ca2+ mobilizing hormone (f) attempt to characterize the mechanism of activation of the endoplasmic reticulum Ca2+ pump by the Ca2+ pump by the Ca2+ mobilizing hormones. Our basic studies are providing techniques to test hypotheses on hormonal regulation of free cytosolic Ca2+ and Ca2+ content in the intracellular stores of pancreatic acinar cells both during and at the termination of cell stimulation.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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General Medicine A Subcommittee 2 (GMA)
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Cedars-Sinai Medical Center
Los Angeles
United States
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