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Role Of Type 4 Phosphodiesterases In Thermoregulation And Salivation In Mice, Abigail Grace Boyd

<strong> Theses and Dissertations </strong>

Type 4 cAMP phosphodiesterases (PDE4s) comprise a family of four isoenzymes, PDE4A to D, that hydrolyze and inactivate the second messenger cAMP. Non/PAN selective PDE4 inhibitors, which inhibit all four subtypes simultaneously, produce many promising therapeutic benefits, such as anti-inflammatory or cognition- and memory-enhancing effects. However, unwanted side effects, principally, nausea, diarrhea, and emesis, have long hampered their clinical and commercial success. Targeting individual PDE4 subtypes has been proposed for developing drugs with an improved safety profile, but which PDE4 subtype(s) is/are actually responsible for nausea and emesis remains ill defined. In mice treated with PAN-selective inhibitors, there is substantial …