Our current understanding of the normal function of salivary gland acinar cells and their role in oral health and disease has improved significantly. However, the precise molecular events -involved in the regulation of salivary gland secretion, growth and development are still poorly understood. Over recent years, the beta-adrenergic receptor mediated events have been shown to play an important role in salivary gland cellular biology, including cell growth and differentiation, energy metabolism, ion transport, protein synthesis, gene expression, DNA synthesis and exocytosis. A better understanding of the actual molecular events involved in beta-adrenergic mediated cellular regulation of normal salivary gland acinar cell function would provide the necessary fundamental information to more fully comprehend the normal molecular and cellular biology of these cells, and the possible molecular basis for the pathogenesis seen in various exocrine diseases of the oral cavity. The long range objective of this research project is to develop new basic scientific information regarding the actual molecular events that are directly controlled within the rat parotid and submandibular acinar cell following beta-adrenergic receptor activation. Our current research objectives are to study more fully an integral membrane phosphoprotein (pp26) which appears to be directly involved in the beta-adrenergic receptor mediated signal transduction pathway(s) following beta-adrenergic receptor stimulation.
Specific aims i nclude the sequencing of both rat parotid and submandibular pp26 phosphoprotein using current protein chemistry-protein sequencing techniques and molecular biology-PCR techniques. Once having sequenced both pp26s, computer-based consensus sequence analysis, and immunocytolocalization studies will be done to determine the biological role of pp26 during beta-adrenergic receptor mediated stimulation. Finally, Western blotting and riboprobe analysis will be utilized to determine the extent of tissue expression of pp26 mRNA and distribution of these phosphoproteins in various organs. These studies should provide important new scientific information regarding the intracellular events that occur following beta-adrenergic receptor stimulation and their role in normal salivary gland cellular and molecular biology.
