Ghrelin receptor signaling in health and disease: a biased view

Joshua D. Gross; Yang Zhou; Lawrence S. Barak; Marc G. Caron

doi:10.1016/j.tem.2022.12.001

Ghrelin receptor signaling in health and disease: a biased view

Joshua D. Gross, Yang Zhou, Lawrence S. Barak, Marc G. Caron

Research output: Contribution to journal › Review article › peer-review

8 Scopus citations

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 (GHSR_1a), has a crucial role in restoring and maintaining metabolic homeostasis during disrupted energy balance. Thus, pharmacological modulation of GHSR_1a bias could offer a promising strategy to treat several metabolism-based disorders. Here, we summarize current evidence supporting GHSR_1a functional selectivity in vivo and highlight recent structural data. We propose that precise determinations of GHSR_1a molecular pharmacology and pathway-specific physiological effects will enable discovery of GHSR_1a drugs with tailored signaling profiles, thereby providing safer and more effective treatments for metabolic diseases.

Original language	English (US)
Pages (from-to)	106-118
Number of pages	13
Journal	Trends in Endocrinology and Metabolism
Volume	34
Issue number	2
DOIs	https://doi.org/10.1016/j.tem.2022.12.001
State	Published - Feb 2023

All Science Journal Classification (ASJC) codes

Endocrinology, Diabetes and Metabolism
Endocrinology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.tem.2022.12.001

Cite this

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title = "Ghrelin receptor signaling in health and disease: a biased view",

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.",

author = "Gross, {Joshua D.} and Yang Zhou and Barak, {Lawrence S.} and Caron, {Marc G.}",

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T1 - Ghrelin receptor signaling in health and disease

T2 - a biased view

AU - Gross, Joshua D.

AU - Zhou, Yang

AU - Barak, Lawrence S.

AU - Caron, Marc G.

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N2 - 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.

AB - 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.

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Ghrelin receptor signaling in health and disease: a biased view

Abstract

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