Although progress has been made in describing a variety of secretory systems and some insights have been made regarding the regulatory mechanisms involved in exocytosis, the cellular control mechanisms and the molecular events involved in exocytosis are still poorly understood. A better understanding of the stimulus-secretion coupling mechanism in exocrine tissue will provide the needed information to more fully comprehend the function and dysfunction of exocrine tissue. We are proposing to study certain aspects of rat parotid amylase secretion. Once having gained additional insight regarding the molecular events involved in rat parotid amylase secretion, we plan to study human tissue, salivary cells from normal patients and from patients with cystic fibrosis, to see if a secretory defect is present in CF tissue. In particular, we are proposing to study the role of cAMP in regulating rat parotid amylase secretion. We intend to: (1) purify and begin to characterize two membrane bound phosphoproteins which are phosphorylated in a Beta-adrenergic receptor depedent manner; (2) further characterize and quantitate the possible role of cAMP-dependent protein kinase in regulating rat parotid amylase secretion; and (3) determine if other cellular proteins are being phosphorylated in a Beta-adrenergic dependent manner. These studies should give new and basic information regarding mucin secretion which may, in turn, provide important data for understanding the possible pathogenesis of cystic fibrosis.
