The composition and secretion of saliva as well as the morphology of parotid and submandibular glands in rats are influenced by beta-adrenoreceptors (beta-AR). Stimulation of these receptors by isoproterenol in vitro or in vivo increases levels of cAMP, protein phosphorylation, secretion, induces hyperplasia in these glands and alters salivary gland-specific gene expression. Our studies are designed to; (i) identify the mechanisms by which information from beta-AR is transmitted to the nucleus and thus regulates these processes and (ii) examine the alterations in gene expression, protein synthesis and gland morphology in salivary gland disease. We primarily have focused on the role(s) of the proto-oncogenes c-fos, c-jun and c-abl in eliciting the beta-AR responses in rat parotid acinar cells (RPAC) and in a salivary cell line (A5). In particular we studied the possible coordinate expression of these proto-oncogenes with salivary gland-specific genes during agonist stimulation, gland development and salivary gland disease. During this reporting period we have demonstrated that; 1) the isoproterenol-inducible c-abl mRNAs represent part of the C-terminal segment of the gene; 2) stimulation of beta-AR in vitro regulates proline-rich protein (PRP), amylase, parotid secretory protein (PSP) and kalikrein synthesis and secretion post-transcriptionally, while in vivo chronic isoproterenol administration alters the transcription rates of these molecules; 3) only short times (5 min) of beta-AR stimulation or exposure to cAMP are needed for the induction of c-fos and c-jun genes in A5 cells; 4) cultured RPAC, for 8 months, maintain some characteristics of their phenotype and; 5) c-myc, c-fos and c-jun expression in the salivary glands of patients with Sjogren's syndrome show a distinctly different pattern.
