Investigating the molecular pharmacology of class A and B G protein-coupled receptors
type: CreativeWork
description: G protein-coupled receptors (GPCRs) possess an inherent ability to bind to an extremely diverse range of ligands and activate multiple downstream signalling pathways. It is becomingly increasingly evident, however, that for many GPCRs, the exact downstream signalling cascade(s), and the extent of activation, often varies in an agonist- and cell type-dependent manner. Receptor signalling can be further influenced by interacting proteins, such as receptor activity-modifying proteins (RAMPs), or internalisation, whereby distinct responses may be propagated by intracellular GPCR populations. Hence, the signalling repertoire subsequent to receptor activation is extremely complex, varying between individual GPCRs and the biological systems in which they are investigated. Here, work is presented investigating the signalling capabilities of the Adenosine A2A receptor (A2AR), the Calcitonin receptor-like receptor (CLR), the Calcitonin receptor (CTR), corticotrophin-releasing factor receptor type 2 (CRFR2) and the growth hormone-releasing hormone receptor (GHRHR). For the A2AR, agonist-mediated cAMP production and β-arrestin recruitment is studied, as well as receptor internalisation. In particular, the effects of small molecule inhibitors of internalisation are investigated with regards to cAMP production, attempting to decipher the importance of receptor internalisation in A2AR-mediated signalling. More specifically, the A2AR is demonstrated to signal in a sustained manner, following agonist stimulation, whilst revealing an inability to recruit β-arrestins or undergo agonist-induced internalisation. Furthermore, the study was expanded to include other Adenosine receptors: the A1R, A2BR and A3R, as well as the β2 adrenoceptor, to allow for comparison between different class A GPCRs. Work pertaining to the CLR begins with an investigation into interactions between a subset of class B GPCRs and RAMPs at the cell surface, with RAMP-receptor interactions revealed to be cell type…
abstract: G protein-coupled receptors (GPCRs) possess an inherent ability to bind to an extremely diverse range of ligands and activate multiple downstream signalling pathways. It is becomingly increasingly evident, however, that for many GPCRs, the exact downstream signalling cascade(s), and the extent of activation, often varies in an agonist- and cell type-dependent manner. Receptor signalling can be further influenced by interacting proteins, such as receptor activity-modifying proteins (RAMPs), or internalisation, whereby distinct responses may be propagated by intracellular GPCR populations. Hence, the signalling repertoire subsequent to receptor activation is extremely complex, varying between individual GPCRs and the biological systems in which they are investigated. Here, work is presented investigating the signalling capabilities of the Adenosine A2A receptor (A2AR), the Calcitonin receptor-like receptor (CLR), the Calcitonin receptor (CTR), corticotrophin-releasing factor receptor type 2 (CRFR2) and the growth hormone-releasing hormone receptor (GHRHR). For the A2AR, agonist-mediated cAMP production and β-arrestin recruitment is studied, as well as receptor internalisation. In particular, the effects of small molecule inhibitors of internalisation are investigated with regards to cAMP production, attempting to decipher the importance of receptor internalisation in A2AR-mediated signalling. More specifically, the A2AR is demonstrated to signal in a sustained manner, following agonist stimulation, whilst revealing an inability to recruit β-arrestins or undergo agonist-induced internalisation. Furthermore, the study was expanded to include other Adenosine receptors: the A1R, A2BR and A3R, as well as the β2 adrenoceptor, to allow for comparison between different class A GPCRs. Work pertaining to the CLR begins with an investigation into interactions between a subset of class B GPCRs and RAMPs at the cell surface, with RAMP-receptor interactions revealed to be cell type…
author: Carvalho, Sabrina
language: eng
keywords: GPCR, Adenosine receptor, A2A, CLR, RAMP, internalisation, signalling
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2021-12
date modified: 2026-07-22T22:24:27Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.84601