G protein-coupled receptors and their signal transduction pathways coupling to functional responses in salivary glands
The importance of saliva is apparent in patients who receive radiation therapy for head and neck cancers. Ionizing radiation often results in salivary gland degeneration that results in xerostomia, leading at times to serious complications which can affect treatment outcome. For example, lack of saliva results in painful tongue and mucosa, problems with taste and phonation, swallowing, chewing, and increased risk of infection.
We are examining alpha-1 adrenergic receptors, which interact with norepinephrine to mediate the actions of the sympathetic nervous system in regulating secretion and activation of mitogen-activated protein kinase pathways. ERK1/2 are important signaling molecules in this pathway and are activated by alpha-1 adrenergic receptors, regulating acinar cell growth and proliferation in salivary glands. Alpha-1 adrenergic receptors consist of three subtypes referred to as the alpha-1A, alpha-1B and alpha-1D adrenergic receptors. The functional significance of subtype-specific activation of various signaling pathways in salivary glands is unknown but is currently being explored in our laboratory.
These studies will identify and characterize novel drug targets that we hope will provide a rational basis for the design of drugs specific for treating salivary gland hypofunction.
o Health Future Foundation Faculty Development Award "Role of Alpha-1 Adrenergic
Receptor Subtypes in the Submandibular Gland". Active (7/05 - 6/07)
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