Ghrelin receptor signaling in health and disease: a biased view

被引：10

作者：

Gross, Joshua D. ^{[1
]}

Zhou, Yang ^{[1
]}

Barak, Lawrence S. ^{[1
]}

Caron, Marc G. ^{[1
]}

机构：

[1] Duke Univ, Dept Cell Biol, Durham, NC 27710 USA

来源：

TRENDS IN ENDOCRINOLOGY AND METABOLISM | 2023年 / 34卷 / 02期

关键词：

HORMONE SECRETAGOGUE RECEPTOR; PROTEIN-COUPLED RECEPTORS; CONSTITUTIVE ACTIVITY; ALLOSTERIC MODULATORS; CIRCULATING GHRELIN; CALORIE RESTRICTION; INSULIN-SECRETION; GLUCOSE-TOLERANCE; PANCREATIC ALPHA; ACYLATED PEPTIDE;

D O I：

10.1016/j.tem.2022.12.001

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

As allosteric complexes, G-protein-coupled receptors (GPCRs) respond to extra -cellular 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 sum-marize 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.

引用

页码：106 / 118

页数：13