The salivary glands and their secretions are vital to the capacity of ixodid ticks to he parasitic and are the major route by which pathogenic organisms and toxins access the vertebrate host. We propose to continue research on the characterization of receptors and signal pathways controlling salivary gland function in an ixodid tick, Amblyomma americanum (L.). The evidence implicating dopamine as a neurotransmitter at the neuroeffector junction and its interaction with a D-1 receptor is compelling; however, the effects of dopamine receptor antagonists on dopamine stimulated fluid secretion suggest that dopamine control is more complex and may utilize multiple receptors. Receptor binding studies, cyclic AMP, and secretion assays will he used to clarify the role of dopamine and dopamine receptors in the salivary glands. Other data indicates the existence of a ligand (neuropeptide from the tick synganglion), which through a receptor mediated interaction, activates phospholipase C (PLC) catalyzed hydrolysis of plasma membrane phosphoinositides. We propose to study the forms and characteristics of PLC. We will also address the question of whether PLC is activated through a receptor tyrosine kinase or GTP-dependent protein. Signalling through phosphatidylcholine breakdown and its relationship, if any, to phosphoinositide turnover will also be investigated. Since salivary secretion is regulated by protein kinase-catalyzed phosphorylation of proteins, we will continue ongoing molecular characterization of protein kinases and their role in controlling salivary gland function. Information about receptors and regulation of cell functions in the salivary glands will provide key insights into factors which enable ticks to be parasitic and their relationship to pathogen transmission to hosts.