growth hormone secretagogue
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2022 ◽  
Vol 23 (2) ◽  
pp. 761
Author(s):  
Magdalena Sustkova-Fiserova ◽  
Chrysostomos Charalambous ◽  
Anna Khryakova ◽  
Alina Certilina ◽  
Marek Lapka ◽  
...  

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.


2021 ◽  
Vol 12 ◽  
Author(s):  
Jing Zhao ◽  
Xinyu Du ◽  
Mingzhu Chen ◽  
Shimin Zhu

Relapse to drug seeking after prolonged abstinence is a major problem in the clinical treatment of drug addiction. The use of pharmacological interventions to disrupt established drug reward memories is a promising strategy for the treatment of drug addiction. A growth hormone secretagogue receptor 1 A antagonist, JMV2959, has been shown to reduce morphine-induced conditioned place preference (CPP) in rats within hours of intervention; thus, JMV2959 is a potential candidate for drug addiction treatment. However, the effect of JMV2959 on reconsolidation to disrupt drug seeking remains unknown. In this study, we assessed the effect of JMV2959 on morphine induced memory reconsolidation to inhibit drug seeking after drug withdrawal. Our results showed that the administration of JMV2959 (6 mg/kg) significantly reduced environmental cue induced CPP, which suggested a preventive effect of JMV2959 on morphine induced memory reconsolidation. Additionally, JMV2959 administration significantly altered the locomotor activity and food and water intake but did not significantly alter the natural reward preference. We concluded that JMV2959 may be an effective candidate to treat drug addiction.


2021 ◽  
Author(s):  
Rebeca Martinez Rodriguez ◽  
Maria Alejandra Fernandez-Trujillo ◽  
Liz Hernandez ◽  
Adrián Page ◽  
Julia Béjar ◽  
...  

Abstract Aquaculture constitutes an alternative source for food production and contributes to the reduction of indiscriminate catch of aquatic organisms from their natural environment (Diaz & Neira, 2005; Beveridge et al., 2013). However, high mortality during larval state remains a challenge in this sector, mainly because of factors like diets and diseases induced by pathogens (Helvik et al., 2009; Stentiford et al., 2017). Therefore, growth and health management is a key strategy for sustainable aquaculture (Martinez et al., 2016a).


2021 ◽  
Vol 15 ◽  
pp. 26-33
Author(s):  
Vanessa Zambelli ◽  
Laura Rizzi ◽  
Paolo Delvecchio ◽  
Elena Bresciani ◽  
Emanuele Rezoagli ◽  
...  

Introduction: Acute respiratory distress syndrome (ARDS) is an acute form of diffuse lung injury characterized by (i) an intense inflammatory response, (ii) increased pulmonary vascular permeability, and (iii) the loss of respiratory pulmonary tissue. In this article we explore the therapeutic potential of hexarelin, a synthetic hexapeptide growth hormone secretagogue (GHS), in an experimental model of ARDS. Hexarelin has anti-inflammatory properties and demonstrates cardiovascular-protective activities including the inhibition of cardiomyocyte apoptosis and cardiac fibrosis, both of which may involve the angiotensin-converting enzyme (ACE) system. Methods: In our experimental model, ARDS was induced by the instillation of 100 mM HCl into the right bronchus; these mice were treated with hexarelin (320 μg/kg, ip) before (Pre) or after (Post) HCl challenge, or with vehicle. Respiratory system compliance, blood gas analysis, and differential cell counts in a selective bronchoalveolar lavage (BAL) were determined 6 or 24 hours after HCl instillation. In an extended study, mice were observed for a subsequent 14 days in order to assess lung fibrosis. Results: Hexarelin induced a significant improvement in lung compliance and a reduction of the number of total immune cells in BAL 24 hours after HCl instillation, accompanied with a lower recruitment of neutrophils compared with the vehicle group. At day 14, hexarelin-treated mice presented with less pulmonary collagen deposition compared with vehicle-treated controls. Conclusions: Our data suggest that hexarelin can inhibit the early phase of the inflammatory response in a murine model of HCl-induced ARDS, thereby blunting lung remodeling processes and fibrotic development.


2021 ◽  
Vol 65 (s1) ◽  
Author(s):  
Giulia Ronchi ◽  
Pierluigi Tos ◽  
Elia Angelino ◽  
Luisa Muratori ◽  
Simone Reano ◽  
...  

Ghrelin is a circulating peptide hormone released by enteroendocrine cells of the gastrointestinal tract as two forms, acylated and unacylated. Acylated ghrelin (AG) binds to the growth hormone secretagogue receptor 1a (GHSR1a), thus stimulating food intake, growth hormone release, and gastrointestinal motility. Conversely, unacylated GHR (UnAG), through binding to a yet unidentified receptor, protects the skeletal muscle from atrophy, stimulates muscle regeneration, and protects cardiomyocytes from ischemic damage. Recently, interest about ghrelin has raised also among neuroscientists because of its effect on the nervous system, especially the stimulation of neurogenesis in spinal cord, brain stem, and hippocampus. However, few information is still available about its effectiveness on peripheral nerve regeneration. To partially fill this gap, the aim of this study was to assess the effect of UnAG on peripheral nerve regeneration after median nerve crush injury and after nerve transection immediately repaired by means of an end-to-end suture. To this end, we exploited FVB1 Myh6/Ghrl transgenic mice in which overexpression of the ghrelin gene (Ghrl) results in selective up-regulation of circulating UnAG levels, but not of AG. Regeneration was assessed by both functional evaluation (grasping test) and morphometrical analysis of regenerated myelinated axons. Results obtained lead to conclude that UnAG could have a role in development of peripheral nerves and during more severe lesions.


2021 ◽  
Vol 9 (21) ◽  
Author(s):  
Marat I. Airapetov ◽  
Sergei O. Eresko ◽  
Andrei A. Lebedev ◽  
Evgenii R. Bychkov ◽  
Petr D. Shabanov

2021 ◽  
Vol 9 (22) ◽  
pp. 1696-1696
Author(s):  
Liang Wu ◽  
Dongliang Li ◽  
Linlin Qin ◽  
Qingliang Wang ◽  
Yuichi Saito ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kiyoshi Chinen ◽  
Naoaki Sakata ◽  
Gumpei Yoshimatsu ◽  
Masafumi Nakamura ◽  
Shohta Kodama

AbstractIslet transplantation is a type of cellular replacement therapy for severe diabetes that is limited by compromising effect on engrafted islets. Trials aiming to improve the function of transplanted islets have also been challenging. This study attempted to elucidate whether regulation of growth hormone secretagogue receptor-1a (GHS-R1a), one of the ghrelin receptors, improve the therapeutic effects of islet transplantation using [D-Lys3]-GHRP-6 (DLS), a specific GHS-R1a antagonist. The therapeutic effects of DLS were assessed in terms of the expression/production of endocrine genes/proteins, insulin-releasing function under glucose stimulation of mouse islets, and outcomes of syngeneic murine islet transplantation with systemic DLS administration. DLS treatment promoted insulin production and suppressed somatostatin production, suggesting that cancelation of the binding between ghrelin and GHS-R1a on β or δ cells improved insulin expression. DLS also promoted the glucose-dependent insulin-releasing function of β cells. However, the therapeutic effect of DLS in islet transplantation was fractional. In conclusion, the GHS-R1a antagonist showed preferable effects in improving the therapeutic outcomes of islet transplantation, including the promotion of insulin-releasing function.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Nan Li ◽  
Na Li ◽  
Fenghua Xu ◽  
Ming Yu ◽  
Zichen Qiao ◽  
...  

Abstract Aim Growth hormone secretagogue receptor 1a (GHS-R1a) is widely distributed in brain including the hippocampus. Studies have demonstrated the critical role of hippocampal ghrelin/GHS-R1a signaling in synaptic physiology, memory and cognitive dysfunction associated with Alzheimer’s disease (AD). However, current reports are inconsistent, and the mechanism underlying memory modulation of GHS-R1a signaling is uncertain. In this study, we aim to investigate the direct impact of selective increase of GHS-R1a expression in dCA1 excitatory/inhibitory neurons on learning and memory. Methods Endogenous GHS-R1a distribution in dCA1 excitatory/inhibitory neurons was assessed by fluorescence in situ hybridization. Cre-dependent GHS-R1a overexpression in excitatory or inhibitory neurons was done by stereotaxic injection of aav-hSyn-DIO-hGhsr1a-2A-eGFP virus in dCA1 region of vGlut1-Cre or Dlx5/6-Cre mice respectively. Virus-mediated GHS-R1a upregulation in dCA1 neurons was confirmed by quantitative RT-PCR. Different behavioral paradigms were used to evaluate long-term memory performance. Results GHS-R1a is distributed both in dCA1 excitatory pyramidal neurons (αCaMKII+) and in inhibitory interneurons (GAD67+). Selective increase of GHS-R1a expression in dCA1 pyramidal neurons impaired spatial memory and object-place recognition memory. In contrast, selective increase of GHS-R1a expression in dCA1 interneurons enhanced long-term memory performance. Our findings reveal, for the first time, a neuronal type-specific role that hippocampal GHS-R1a signaling plays in regulating memory. Therefore, manipulating GHS-R1a expression/activity in different subpopulation of neurons may help to clarify current contradictory findings and to elucidate mechanism of memory control by ghrelin/GHS-R1a signaling, under both physiological and pathological conditions such as AD.


2021 ◽  
Vol 35 (23) ◽  
Author(s):  
Moses Philip ◽  
Abdul Khader Karakka Kal ◽  
Michael Benedict Subhahar ◽  
Zubair Perwad ◽  
Tajudheen K. Karatt

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