Current treatment for hyposalivation includes the users of muscarinic cholinergic agonists. Unfortunately, the currently used drugs are not specific for muscarinic receptor subtypes causing various adverse secondary effects. As more specific drugs are under development, it is crucial to investigate and understand the receptors' behavior upon agonist exposure in order to take advantage of the incoming technology. Unique sequences of 240-375 base pairs for m1, m2, and m3 receptors have been cloned. Each clone was sequenced and verified. From these, RNA probes will be made and use in Northern Blot analysis and in situ hybridization studies to localize m1 and m3 receptors in the sublingual gland. M2 will be used as a negative control. After localization of the receptors, functional pharmacological studies will be performed where the receptors will be exposed to various concentrations of the muscarinic agonists at different time intervals. Further, the possibility of receptor sequestration and downregulation upon agonist exposure will be investigated; the mechanisms responsible for these events will be defined. The time course for the recovery of receptor expression and function will also be determined. KEY WORDS: Muscarinic receptors, rat sublingual glands
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