Studies of the physiology and biochemistry and control of salivary secretion in feeding ixodid ticks will be continued. After reception of the primary stimulus (dopamine), the salivary glands utilize cyclic AMP (cAMP) and Ca2+ to help modulate cell activity during secretion. Little is known about how Ca2+ is mobilized during salivary gland function. Therefore, a role for the metabolism of plasma membrane phosphoinositides in signal transduction in the salivary glands will be studied. The question of whether enhanced hydrolysis of plasma membrane phosphatidylinositol 4,5-trisphosphate after agonist-receptor interaction mediates mobilization of intracellular Ca2+ will be explored. The physiological agonists of salivary gland phosphoinositide metabolism will be identified. The ability of these agonists to modulate salivary secretion with and without other known agonists of secretion i.e. dopamine and cAMP will be studied. The possible relationship between agonist-stimulated turnover of phosphoinositides and production and secretion of prostaglandins will be investigated. Possible protein kinase C activity in the salivary glands and its activation by another product of phosphoinositide metabolism, diacylglycerol and phorbol esters will be investigated. The """"""""second messenger"""""""" role for cAMP has been studied but little is known about functions of phosphoproteins. Therefore, the phosphoprotein phosphorylated by cAMP-dependent protein kinase to modulate protein phosphatase activity and its relationship to inhibition of protein phosphatase by Ca2+ will be investigated. Information about how metabolic pathways regulate secretion, either directly or indirectly, should shed light on synthesis and secretion of substances that contribute to a tick's successful feeding and their ability to vector pathogens. Ultimately the results may be useful for applied biology. Interference with an essential point in a metabolic pathway controlling salivary secretion could provide a new approach to tick control or the pathogens they vector.
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