Novel heteromeric receptors: ghrelin receptors and dopamine receptors working together
Ghrelin is a naturally occurring hormone that had been thought to be a transmitter in the central nervous system (CNS). Some years ago we discovered that ghrelin is a powerful CNS-acting stimulant of defecation in animal models and humans. A striking conclusion from our discoveries is that the strong stimulation of defecation by ghrelin agonists is independent of ghrelin, which we discovered to be absent from the CNS. Our data indicates that the physiological activation of the ghrelin receptor, GHSR, is through dopaminergic transmission acting at a combined GHSR/dopamine 2 receptor (DRD2).
In this project we are investigating how ghrelin and dopamine receptor agonists act and interact at this receptor complex in biophysical systems, isolated cells, native cells and whole animals. We will investigate the relevance of our discoveries for treatment of constipation in two disease models.
Take part in this project
Students who are applying to study at The Florey can register their interest in this project. Refer to our step-by-step guide to help you with your application.
Furness JB, Pustovit RV, Syder AJ, Ringuet MT, Yoo EJ, Fanjul A, Wykosky J, Fothergill LJ, Whitfield EA, Furness SGB (2021), ‘Dopamine and ghrelin receptor co-expression and interaction in the spinal defecation centres’, Neurogastroenterology & Motility, 33, e14051, doi:10.1111/nmo.14051
Ringuet MT, Furness JB, Furness SGB (2022), ‘G protein-coupled receptor interactions and modification of signalling involving the ghrelin receptor’, GHSR1a, Journal of Neuroendocrinology 34, e13077, doi:10.1111/jne.13077