Date of Award

6-1-2011

Document Type

Thesis

Degree Name

M.S.

Department

Biological Sciences

First Advisor

Joseph K. Angleson, Ph.D.

Second Advisor

Robert Dores

Third Advisor

Nancy Lorenzon

Fourth Advisor

Dwight Smith

Keywords

Inhibitors of cAMP phosphodiestereses, Modulation of calcium influx, Endocrine cells

Abstract

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.

Publication Statement

Copyright is held by the author. User is responsible for all copyright compliance.

Provenance

Received from ProQuest

Rights holder

Colette Crane

File size

68 p.

File format

application/pdf

Language

en

Discipline

Cellular biology

Included in

Biology Commons

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