Alexandria Digital Research Library

Pharmacodynamics of Pseudopterosin A Interaction with Adenosine A2B Receptors in Stimulation of Cell Proliferation

Author:
Day, Daniel Richard
Degree Grantor:
University of California, Santa Barbara. Ecology, Evolution & Marine Biology
Degree Supervisor:
Robert S. Jacobs
Place of Publication:
[Santa Barbara, Calif.]
Publisher:
University of California, Santa Barbara
Creation Date:
2011
Issued Date:
2011
Topics:
Chemistry, Biochemistry, Health Sciences, Pharmacy, and Health Sciences, Pharmacology
Keywords:
Adenosine Receptors
Wound Healing
Pseudopterosin
Cyclic AMP
Angiogenesis
Natural Products
Genres:
Dissertations, Academic and Online resources
Dissertation:
Ph.D.--University of California, Santa Barbara, 2011
Description:

Pseudopterosins are known anti-inflammatory and anti-microbial agents, isolated from the soft coral, Pseudopterogorgia elisabethae. This study implicates pseudopterosins as activators of cell proliferation in human umbilical vein endothelial cells (HUVEC), a cellular model of angiogenesis. A hydroxypropyl-beta-cyclodextrin (HPbetaCD) formulation of pseudopterosin A (PsA) elicited a 25% increase in cell proliferation (EC50 = 1.34 x10-8 M) in growth factor depleted HUVEC lines. This constitutes a >200 fold increase in potency over DMSO formulations. This increase in specific activity of the drug may result from constraints placed upon PsA orientation in HPbetaCD allowing for more efficient presentation to the receptor. This study demonstrates that the effect of PsA is mediated through inhibition of adenosine A2B receptors which leads to decreased synthesis of cAMP and that this effect can be reversed with a selective A 2 agonist, CV-1808. In addition, evidence is presented that PsA can induce protein kinase B (AKT) phosphorylation which has been shown to activate proliferation via the phosphatidylinositol 3-kinase (PI3K) pathway. Collectively, this indicates that pseudopterosins are promising compounds for adenosine receptor mediated pathologies.

Physical Description:
1 online resource (127 pages)
Format:
Text
Collection(s):
UCSB electronic theses and dissertations
ARK:
ark:/48907/f3h12zx7
ISBN:
9781267194077
Catalog System Number:
990037518410203776
Rights:
Inc.icon only.dark In Copyright
Copyright Holder:
Daniel Day
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