Date of Award

2016

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Pharmacology and Experimental Therapeutics

Abstract

The overall objective of this thesis work is to determine the mechanism by which celecoxib modulates Kv7 potassium channels in vascular smooth muscle cells. The central hypothesis of the project is that celecoxib modulates Kv7 potassium channels in vascular smooth muscle cells through inhibition of phosphodiesterase 4 (PDE4, which catalyzes the breakdown of cyclic adenosine monophosphate (cAMP)), thereby activating a cAMP/protein kinase A (PKA) signaling pathway. The aims of this thesis targeted different points in the cAMP/PKA pathway with pharmacological interventions using whole cell perforated patch clamp electrophysiology and biochemical methods.

The data suggest multiple mechanisms by which celecoxib could be eliciting its Kv7 channel activation with better evidence suggesting requirement of a critical residue for channel activation than an indirect PDE4/cAMP/PKA-dependent pathway. Further work is needed to determine celecoxib’s exact mechanism of Kv7 channel activation.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

Included in

Pharmacology Commons

Share

COinS