Fluorescent Probes for Monitoring Ligand Binding and Receptor Trafficking and Internalisation

The Neurokinin 1 receptor (NK1R) is associated with neurogenic inflammation and nociceptive transmission through signal propagation by the endogenous agonist, substance P. Internalised NK1R in the endosome has a distinct signalling profile from that at the cell surface, resulting in unique pathophysiological outcomes. Therefore, endosomal populations of NK1R may be considered distinct therapeutic targets. The lack of clinical success of current NK1R antagonists, may be due to their inability to target endosomal NK1R. This thesis explores the utility of fluorescent probes for assessing ligand distribution and interaction with endosomal NK1R, and for developing tools to screen for endosomal NK1R ligands.