The overall goal of this continuing program is to determine the intracellular signalling processes responsible for the pancreatic enzyme secretion stimulated by the agonists, cholecystokinin, acetylcholine and bombesin. These agents regulate various calcium transports and activate metabolism of various phospholipid classes in the pancreatic acinar cell. Many of these processes have been implicated in the secretory process.
The aims for the next period of this program will be to establish the mechanism of the following processes regulated by the agonist: plasma membrane calcium influx; transient (or quantal) release of calcium from the intracellular agonist-sensitive pool; uptake of calcium into the pool; phospholipase A-mediated breakdown of phosphatidylcholine; and intercellular communication between cells of the acinus. In addition, to determining the mechanisms regulating these processes, we propose experiments to establish their specific roles in the secretory process. The experiments will be performed using dispersed pancreatic acini from guinea pigs and rats. They will involve measurements of calcium transports; various phospholipids and their metabolites; and secretion of digestive enzymes. The results will provide a model of the initial intracellular signalling events that mediate secretion and will provide a basis for investigation of the mechanism of pancreatic disorders.
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