Abstract
Abstract There is a growing recognition that needs more to be done to ensure that research contributes to better health services and patient outcomes. Stakeholder engagement in research, including co-production, has been identified as a promising mechanism for improving the value, relevance and utilization of research. This article presents findings from a prospective study which explored the impact of stakeholder engagement in a 3-year European tobacco control research project. That research project aimed to engage stakeholders in the development, testing and dissemination of a return-on-investment tool across five EU countries (the Netherlands, Spain, Hungary, Germany and the UK). The prospective study comprised interviews, observations and document review. The analysis focused on the extent to which the project team recognized, conceptualized and operationalized stakeholder engagement over the course of the research project. Stakeholder engagement in the European research project was conceptualized as a key feature of pre-designated spaces within their work programme. Over the course of the project, however, the tool development work and stakeholder engagement activities decoupled. While the modelling and tool development became more secluded, stakeholder engagement activities subtly transformed from co-production, to consultation, to something more recognizable as research participation. The contribution of this article is not to argue against the potential contribution of stakeholder engagement and co-production, but to show how even well-planned engagement activities can be diverted within the existing research funding and research production systems where non-research stakeholders remain at the margins and can even be seen as a threat to academic identify and autonomy.
Highlights
Agonist bias occurs when different ligands produce distinct signalling outputs when acting at the same receptor
Using human endothelial cells which endogenously express the adrenomedullin 1 (AM1) receptor, we demonstrate that biased agonism is present and has a fundamental role in the function of peptide hormones acting on primary human cells
While there are many reports of biased agonism for G protein-coupled receptors (GPCRs) in recombinant systems (e.g.19–21), few examples have been documented in primary human cells
Summary
Agonist bias occurs when different ligands produce distinct signalling outputs when acting at the same receptor. By switching the receptor-activity modifying protein (RAMP) associated with CLR we can “re-route” the physiological pathways activated by endogenous agonists calcitonin gene-related peptide (CGRP), adrenomedullin (AM) and adrenomedullin 2 (AM2). When co-expressed with one of three receptor-activity modifying proteins, (RAMPs), it can be activated by distinct endogenous agonists; calcitonin-gene related polypeptide (CGRP), adrenomedullin (AM) and adrenomedullin 2/intermedin (AM2) This makes it a good system to investigate the role of bias for endogenous ligands. Beyond the Gα subunits CLR has been reported to couple to β-arrestins[13] inducing internalisation, it has been suggested that this interaction can lead to its own signalling events possibly promoting cell proliferation[14] Despite this high potential for agonist-induced pleiotropy, CLR remains most closely associated with adenylyl cyclase activation and generation of cAMP. We chose to focus on RAMP1 and RAMP2 as the CGRP and AM1 receptors are the best described
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