Return to search

Characterization of the Signaling Properties of FLAG Tagged EP2 and EP4 Prostanoid Receptors

Class of 2009 Abstract / OBJECTIVES: To develop a novel characterization system utilizing immunofluorescent FLAG tagged EP2 and EP4 receptors to assist in the explanation of their unique cell signaling properties for exploitation in future drug development design.
METHODS: Plasmids were obtained and isolated that contained cDNAs encoding FLAG-tagged EP2 and EP4 receptors for transient expression in HEK-293 cells. The sequences of these plasmids were confirmed by restriction enzyme analysis and DNA sequencing. Transfected cells were treated with vehicle, PGE2 or forskolin to assess appropriate receptor functionality based on cAMP induction. RESULTS: The two PGE2 receptor subtypes, EP2 and EP4, are similar in their activation of adenylyl cyclase (AC) and subsequent up regulation of cAMP production. These receptors differ, however, in that EP2 more efficiently stimulates cAMP production and EP4 signaling involves the activation of phosphatidylinositol 3-kinase (PI3K) and extracellular signal related kinases (ERKs). The PGE2- treated cells responded as predicted with intracellular production of cAMP, with the EP2 receptor responding more efficiently than the EP4 receptor.
CONCLUSIONS: The intent is for these cells to be used as a novel assay system for the development of future selective EP2 and EP4 agonists. This research could potentially benefit in selectively targeting EP2 or EP4 pathways linked to prevalent ailments such as pain, fever, inflammation, possibly cancer or bone growth.

Identiferoai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/623990
Date January 2009
CreatorsDanielson, Kathryn, Ustic, Sean
ContributorsRegan, John W., College of Pharmacy, The University of Arizona
PublisherThe University of Arizona.
Source SetsUniversity of Arizona
Languageen_US
Detected LanguageEnglish
Typetext, Electronic Report
RightsCopyright © is held by the author.

Page generated in 0.0021 seconds