Date of Award
Joseph K. Angleson, Ph.D.
Inhibitors of cAMP phosphodiestereses, Modulation of calcium influx, Endocrine cells
Inhibitors of cAMP phosphodiestereses (PDEs) promoted an increase in intracellular [cAMP]c and an influx of Ca2+, in both MMQ pituitary cells and α-Pancreatic cells. The specific targets for PDEs and the domains of PDEs are still unknown. Pituitary MMQ cells were used as a model to test modulation of calcium influx through the L-type calcium channel with PDE inhibitors. cAMP analogs were used to determine cAMP molecular targets. 8-cpt-cAMP initiated an Epac mediated pathway and had strong effects on calcium influx in the cell; suggesting, a relatively strong cAMP target. Experiments of α-Pancreatic cells were done in 2mM glucose and 8mM glucose to stimulate hypoglycemia and resting states respectively. Ca2+ induced Ca2+ release (CICR) was observed when αMSH was applied with the three PDE inhibitors. When αMSH was applied without a PDE inhibitor there was no increase in [cAMP]c, suggesting a micro domain. Extracellular solutions of 2mM glucose with PDE inhibitors such as Milironone, there was influx through N-type and L-type channels and then steady CICR. Rolipram decreased the amount of [Ca2+]c influx compared to the control, suggesting an inhibitory effect. PDE locations within the cell dictate the level of [cAMP]c increase and the influx of [Ca2+]c.
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Crane, Colette, "cAMP and Calcium Interactions in Endocrine Cells" (2011). Electronic Theses and Dissertations. 145.
Received from ProQuest