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Pharmacological characterisation of the hP2Y11 and xlP2Y11 receptors.

Drew, C.M.; (2006) Pharmacological characterisation of the hP2Y11 and xlP2Y11 receptors. Doctoral thesis , University of London. Green open access

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Extracellular nucleotides and nucleosides are important signalling molecules that exert a diverse range of physiological responses throughout the body. These chemical messengers often transduce their effects through interaction with specific cell surface receptors called purinoceptors. The P2Y purinoceptor family binds extracellular nucleotides, principally ATP, ADP, UTP and UDP. Conformational change of the P2Y purinoceptors upon ligand binding conveys a signal to intracellular heterotrimeric G proteins, which are activated, transducing the signal further downstream by acting at different effector enzymes to influence second messenger production. In this thesis I present the first pharmacological characterisation of a non-manurtalian P2Yn receptor orthologue, Xenopus laevis P2Yn (XlP2Yn), and extend the pharmacological profile of the human P2Yn receptor (hP2Yn). Second messenger assays were employed to record the intracellular cyclic AMP (cAMP) accumulation and Ca2+ mobilisation generated by both the human and Xenopus laevis P2Y receptors in response to various P2Y agonists and antagonists. In a manner similar to its human orthologue, I have shown that XlP2Yn is activated by nucleotides and nucleotide analogues, mobilising calcium from intracellular stores, and increasing cAMP production through the activation of adenylyl cyclase. When compared to previously published data, XlP2Yn exhibits a novel rank order of agonist and antagonist potency, revealing a receptor functionally similar but pharmacologically distinct from both the human and canine P2Yn receptor orthologues (hP2Yn and cP2Yn).

Type: Thesis (Doctoral)
Title: Pharmacological characterisation of the hP2Y11 and xlP2Y11 receptors.
Identifier: PQ ETD:591941
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: https://discovery.ucl.ac.uk/id/eprint/1444632
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