Complexes of Ghrelin GHS-R1a, GHS-R1b, and Dopamine D<sub>1</sub>Receptors Localized in the Ventral Tegmental Area as Main Mediators of the Dopaminergic Effects of Ghrelin

Navarro, Gemma; Rea, William; Quiroz, César; Moreno, Estefanía; Gomez, Devan M.; Wenthur, Cody J.; Casadó, Vicent; Leggio, Lorenzo; Hearing, Matthew; Ferré, Sergi

doi:10.1523/jneurosci.1151-21.2021

Cited by 16 publications

(13 citation statements)

References 89 publications

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“…Ghrelin is a gut peptide that is mainly produced in the stomach and acts as a potent stimulator of appetite and food intake 10,69,70 . It is known that ghrelin heightens reward sensitivity and promotes the intake of highly palatable foods by acting on the mesolimbic dopaminergic pathway, thereby opposing the effects of leptin and insulin 28,69,71,72 . In obesity, altered circulating ghrelin levels have been reported (both upregulation and downregulation compared to healthy controls), although most evidence points towards lower levels in obesity 73 .…”

Section: Glucocorticoids Appetite‐regulating Hormones and Eating Beha...mentioning

confidence: 99%

Glucocorticoids, stress and eating: The mediating role of appetite‐regulating hormones

et al. 2022

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Disrupted hormonal appetite signaling plays a crucial role in obesity as it may lead to uncontrolled reward-related eating. Such disturbances can be induced not only by weight gain itself but also by glucocorticoid overexposure, for example, due to chronic stress, disease, or medication use. However, the exact pathways are just starting to be understood. Here, we present a conceptual framework of how glucocorticoid excess may impair hormonal appetite signaling and, consequently, eating control in the context of obesity. The evidence we present suggests that counteracting glucocorticoid excess can lead to improvements in appetite signaling and may therefore pose a crucial target for obesity prevention and treatment. In turn, targeting hormonal appetite signals may not only improve weight management and eating behavior but may also decrease detrimental effects of glucocorticoid excess on cardio-metabolic outcomes and mood. We conclude that gaining a better understanding of the relationship between glucocorticoid excess and circulating appetite signals will contribute greatly to improvements in personalized obesity prevention and treatment.

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Section: Glucocorticoids Appetite‐regulating Hormones and Eating Beha...mentioning

confidence: 99%

Glucocorticoids, stress and eating: The mediating role of appetite‐regulating hormones

et al. 2022

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“…For example, a PubMed search performed in July 2022 for the terms “GHSR”, “GHS‐R1a”, “GHS‐R”, “GHSR‐1a” and “ghrelin receptor" retrieved 1199, 2917, 568, 135 and 1139 results, respectively. Notably, GHSR is known to display a variety of ligand‐independent actions, via either its constitutive activity or interaction with other G protein coupled receptors 35,36 . As mentioned below, GHSR also serves as the receptor for liver‐expressed antimicrobial peptide 2 (LEAP2), which is a GHSR antagonist and inverse agonist 37,38 .…”

Section: The Terminology For the Receptormentioning

confidence: 99%

“…Notably, GHSR is known to display a variety of ligand-independent actions, via either its constitutive activity or interaction with other G protein coupled receptors. 35,36 As mentioned below, GHSR also serves as the receptor for liverexpressed antimicrobial peptide 2 (LEAP2), which is a GHSR antagonist and inverse agonist. 37,38 Thus, the term "ghrelin receptor" appears too narrow.…”

Section: Despite a 2005 Report Proposing The Designation "Ghrelin Rec...mentioning

confidence: 99%

Toward a consensus nomenclature for ghrelin, its non‐acylated form, liver expressed antimicrobial peptide 2 and growth hormone secretagogue receptor

Perelló

Dickson

Zigman

et al. 2022

J Neuroendocrinology

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The stomach‐derived octanoylated peptide ghrelin was discovered in 1999 and recognized as an endogenous agonist of the growth hormone secretagogue receptor (GHSR). Subsequently, ghrelin has been shown to play key roles in controlling not only growth hormone secretion, but also a variety of other physiological functions including, but not limited to, food intake, reward‐related behaviors, glucose homeostasis and gastrointestinal tract motility. Importantly, a non‐acylated form of ghrelin, desacyl‐ghrelin, can also be detected in biological samples. Desacyl‐ghrelin, however, does not bind to GHSR at physiological levels, and its physiological role has remained less well‐characterized than that of ghrelin. Ghrelin and desacyl‐ghrelin are currently referred to in the literature using many different terms, highlighting the need for a consistent nomenclature. The variability of terms used to designate ghrelin can lead not only to confusion, but also to miscommunication, especially for those who are less familiar with the ghrelin literature. Thus, we conducted a survey among experts who have contributed to the ghrelin literature aiming to identify whether a consensus may be reached. Based on the results of this consensus, we propose using the terms “ghrelin” and “desacyl‐ghrelin” to refer to the hormone itself and its non‐acylated form, respectively. Based on the results of this consensus, we further propose using the terms “GHSR” for the receptor, and “LEAP2” for liver‐expressed antimicrobial peptide 2, a recently recognized endogenous GHSR antagonist/inverse agonist.

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“…Furthermore, another variant of the ghrelin receptor, GHS-R1B, forms heterodimers/oligomeric complexes with the GHS-R1A and acts as a dual modulator of its functions [ 58 , 76 ]. In actual fact, (acyl-)ghrelin does not bind to the GHS-R1B; nevertheless, this receptor subtype not only determines the efficacy of ghrelin-induced, GHS-R1A-mediated signaling but also seems to determine the ability of GHS-R1A to form oligomeric complexes with other receptors (e.g., D1R), promoting profound qualitative changes in ghrelin-induced signaling [ 47 , 76 , 77 ]. However, the functional role of GHS-R1B still remains much less explored [ 74 , 78 , 79 ].…”

Section: Introductionmentioning

confidence: 99%

“…The strong constitutive activity of the GHS-R1A and its aforementioned ability to heterodimerize with the D1R/D2R in the VTA possibly alter the sensitivity of the mesolimbic dopamine system. Central GHS-R1A receptors are frequently colocalized with dopaminergic and cholinergic receptors [ 42 , 57 ], and it is believed that midbrain functional interactions between these receptors amplify the dopaminergic signaling in the VTA neurons and stimulate the overflow of dopamine in the NAC [ 76 , 82 , 83 ]. The systemic and central (into the VTA) administration of acyl-ghrelin induced the dopamine release in the NAC (shell) and locomotor hyperactivity in rodents [ 61 , 64 , 82 , 84 , 85 ].…”

Section: Introductionmentioning

confidence: 99%

The Role of Ghrelin/GHS-R1A Signaling in Nonalcohol Drug Addictions

Sustkova-Fiserova

Charalambous

Khryakova

et al. 2022

IJMS

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Drug addiction causes constant serious health, social, and economic burden within the human society. The current drug dependence pharmacotherapies, particularly relapse prevention, remain limited, unsatisfactory, unreliable for opioids and tobacco, and even symptomatic for stimulants and cannabinoids, thus, new more effective treatment strategies are researched. The antagonism of the growth hormone secretagogue receptor type A (GHS-R1A) has been recently proposed as a novel alcohol addiction treatment strategy, and it has been intensively studied in experimental models of other addictive drugs, such as nicotine, stimulants, opioids and cannabinoids. The role of ghrelin signaling in these drugs effects has also been investigated. The present review aims to provide a comprehensive overview of preclinical and clinical studies focused on ghrelin’s/GHS-R1A possible involvement in these nonalcohol addictive drugs reinforcing effects and addiction. Although the investigation is still in its early stage, majority of the existing reviewed experimental results from rodents with the addition of few human studies, that searched correlations between the genetic variations of the ghrelin signaling or the ghrelin blood content with the addictive drugs effects, have indicated the importance of the ghrelin’s/GHS-R1As involvement in the nonalcohol abused drugs pro-addictive effects. Further research is necessary to elucidate the exact involved mechanisms and to verify the future potential utilization and safety of the GHS-R1A antagonism use for these drug addiction therapies, particularly for reducing the risk of relapse.

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Complexes of Ghrelin GHS-R1a, GHS-R1b, and Dopamine D₁Receptors Localized in the Ventral Tegmental Area as Main Mediators of the Dopaminergic Effects of Ghrelin

Abstract: Complexes of ghrelin GHS-R1a, GHS-R1b and dopamine D 1 receptors localized in the ventral tegmental area as main mediators of the dopaminergic effects of ghrelin

Cited by 16 publications

References 89 publications

Glucocorticoids, stress and eating: The mediating role of appetite‐regulating hormones

Glucocorticoids, stress and eating: The mediating role of appetite‐regulating hormones

Toward a consensus nomenclature for ghrelin, its non‐acylated form, liver expressed antimicrobial peptide 2 and growth hormone secretagogue receptor

The Role of Ghrelin/GHS-R1A Signaling in Nonalcohol Drug Addictions

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Complexes of Ghrelin GHS-R1a, GHS-R1b, and Dopamine D1Receptors Localized in the Ventral Tegmental Area as Main Mediators of the Dopaminergic Effects of Ghrelin

Abstract: Complexes of ghrelin GHS-R1a, GHS-R1b and dopamine D 1 receptors localized in the ventral tegmental area as main mediators of the dopaminergic effects of ghrelin

Cited by 16 publications

References 89 publications

Glucocorticoids, stress and eating: The mediating role of appetite‐regulating hormones

Glucocorticoids, stress and eating: The mediating role of appetite‐regulating hormones

Toward a consensus nomenclature for ghrelin, its non‐acylated form, liver expressed antimicrobial peptide 2 and growth hormone secretagogue receptor

The Role of Ghrelin/GHS-R1A Signaling in Nonalcohol Drug Addictions

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Product

Resources

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Complexes of Ghrelin GHS-R1a, GHS-R1b, and Dopamine D₁Receptors Localized in the Ventral Tegmental Area as Main Mediators of the Dopaminergic Effects of Ghrelin