Ghrelin receptor signaling in health and disease: a biased view

Trends Endocrinol Metab. 2023 Feb;34(2):106-118. doi: 10.1016/j.tem.2022.12.001. Epub 2022 Dec 24.

Abstract

As allosteric complexes, G-protein-coupled receptors (GPCRs) respond to extracellular stimuli and pleiotropically couple to intracellular transducers to elicit signaling pathway-dependent effects in a process known as biased signaling or functional selectivity. One such GPCR, the ghrelin receptor (GHSR1a), has a crucial role in restoring and maintaining metabolic homeostasis during disrupted energy balance. Thus, pharmacological modulation of GHSR1a bias could offer a promising strategy to treat several metabolism-based disorders. Here, we summarize current evidence supporting GHSR1a functional selectivity in vivo and highlight recent structural data. We propose that precise determinations of GHSR1a molecular pharmacology and pathway-specific physiological effects will enable discovery of GHSR1a drugs with tailored signaling profiles, thereby providing safer and more effective treatments for metabolic diseases.

Keywords: GHSR(1a); GPCR; biased signaling; functional selectivity; ghrelin.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ghrelin / metabolism
  • Humans
  • Receptors, Ghrelin* / genetics
  • Receptors, Ghrelin* / metabolism
  • Signal Transduction* / physiology

Substances

  • Receptors, Ghrelin
  • Ghrelin