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Title: The signalling properties of A1:P2Y1 receptor heteromers formed at physiological expression levels
Author: Cai, Q.
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2013
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Extracellular purine and pyrimidine nucleosides and nucleotides stimulate signalling responses via a family of G protein-coupled receptors (GPCR), known as purinergic receptors, to play essential roles in a diverse range of vital physiological functions. A heteromeric purinergic receptor, comprising the A1 adenosine and P2Y1 receptor subtypes has previously been reported in an overexpressing recombinant system using human embryonic kidney 293T cells, where activation by a P2Y1R agonist (ADPβS) induced an A1Rmediated Gai signalling response. In this thesis I present the first characterisation of the signalling properties of the recombinant human A1R:P2Y1R heteromeric receptor expressed at physiological expression levels, which was achieved by selecting a clonal cell line stably expressing the human A1 adenosine receptor in the Chinese hamster ovary cell line, CHO.K1, which expresses an endogenous P2Y1 receptor. In addition to demonstrating that the A1R:P2Y1R is activated by the endogenous P2Y1 agonist ADP to produce a Gai response, I have shown that ADP also elicits a biphasic calcium (Gaq) response, with the lower affinity site corresponding to the A1R:P2Y1R. The Gai response requires a constitutively active A1R and is inhibited by both A1R and P2Y1R antagonists. The Gaq response of the heteromeric receptor is elicited by both wild type and constitutively active A1 receptors and is not inhibited by any of the antagonists tested. Preliminary experiments to use Bimolecular Fluorescence Complementation to investigate the formation of A1R:P2Y1R in vivo were initiated.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available