scholarly journals Potential metabolic and behavioural roles of the putative endocannabinoid receptors GPR18, GPR55 and GPR119 in feeding

2019 ◽  
Vol 17 (10) ◽  
pp. 947-960 ◽  
Author(s):  
Ricardo E. Ramírez-Orozco ◽  
Ricardo García-Ruiz ◽  
Paula Morales ◽  
Carlos M. Villalón ◽  
J. Rafael Villafán-Bernal ◽  
...  
Keyword(s):  
Cannabinoid Receptors ◽  
Potential Role ◽  
Therapeutic Potential ◽  
Eating Behaviour ◽  
Endocannabinoid System ◽  
G Protein Coupled Receptors ◽  
Know How ◽  
Feeding Control ◽  
G Protein Coupled

: Endocannabinoids are ancient biomolecules involved in several cellular (e.g., metabolism) and physiological (e.g., eating behaviour) functions. Indeed, eating behaviour alterations in marijuana users have led to investigate the orexigenic/anorexigenic effects of cannabinoids in animal/ human models. This increasing body of research suggests that the endocannabinoid system plays an important role in feeding control. Accordingly, within the endocannabinoid system, cannabinoid receptors, enzymes and genes represent potential therapeutic targets for dealing with multiple metabolic and behavioural dysfunctions (e.g., obesity, anorexia, etc.). Paradoxically, our understanding on the endocannabinoid system as a cellular mediator is yet limited. For example: (i) only two cannabinoid receptors have been classified, but they are not enough to explain the pharmacological profile of several experimental effects induced by cannabinoids; and (ii) several orphan G protein-coupled receptors (GPCRs) interact with cannabinoids and we do not know how to classify them (e.g., GPR18, GPR55 and GPR119; amongst others). : On this basis, the present review attempts to summarize the lines of evidence supporting the potential role of GPR18, GPR55 and GPR119 in metabolism and feeding control that may explain some of the divergent effects and puzzling data related to cannabinoid research. Moreover, their therapeutic potential in feeding behaviour alterations will be considered.

scholarly journals Expression and Function of the Endocannabinoid System in the Retina and the Visual Brain

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Jean-François Bouchard ◽  
Christian Casanova ◽  
Bruno Cécyre ◽  
William John Redmond
Keyword(s):  
Visual Processing ◽  
Metabolic Regulation ◽  
Cannabinoid Receptors ◽  
Endocannabinoid System ◽  
G Protein Coupled Receptors ◽  
Retinal Diseases ◽  
Pain Anxiety ◽  
Pharmacological Targets ◽  
And Function ◽  
G Protein Coupled

Endocannabinoids are important retrograde modulators of synaptic transmission throughout the nervous system. Cannabinoid receptors are seven transmembrane G-protein coupled receptors favoringGi/oprotein. They are known to play an important role in various processes, including metabolic regulation, craving, pain, anxiety, and immune function. In the last decade, there has been a growing interest for endocannabinoids in the retina and their role in visual processing. The purpose of this review is to characterize the expression and physiological functions of the endocannabinoid system in the visual system, from the retina to the primary visual cortex, with a main interest regarding the retina, which is the best-described area in this system so far. It will show that the endocannabinoid system is widely present in the retina, mostly in the through pathway where it can modulate neurotransmitter release and ion channel activity, although some evidence also indicates possible mechanisms via amacrine, horizontal, and Müller cells. The presence of multiple endocannabinoid ligands, synthesizing and catabolizing enzymes, and receptors highlights various pharmacological targets for novel therapeutic application to retinal diseases.

scholarly journals Gs-coupled GPCR signalling in AgRP neurons triggers sustained increase in food intake

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Ken-ichiro Nakajima ◽  
Zhenzhong Cui ◽  
Chia Li ◽  
Jaroslawna Meister ◽  
Yinghong Cui ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Potential Role ◽  
G Protein Coupled Receptors ◽  
Signalling Cascades ◽  
Treatment Of Obesity ◽  
G Protein Coupled ◽  
Stimulation Of ◽  
Sustained Increase

Abstract Agouti-related peptide (AgRP) neurons of the hypothalamus play a key role in regulating food intake and body weight, by releasing three different orexigenic molecules: AgRP; GABA; and neuropeptide Y. AgRP neurons express various G protein-coupled receptors (GPCRs) with different coupling properties, including Gs-linked GPCRs. At present, the potential role of Gs-coupled GPCRs in regulating the activity of AgRP neurons remains unknown. Here we show that the activation of Gs-coupled receptors expressed by AgRP neurons leads to a robust and sustained increase in food intake. We also provide detailed mechanistic data linking the stimulation of this class of receptors to the observed feeding phenotype. Moreover, we show that this pathway is clearly distinct from other GPCR signalling cascades that are operative in AgRP neurons. Our data suggest that drugs able to inhibit this signalling pathway may become useful for the treatment of obesity.

scholarly journals Role of Cannabinoid Receptors in Psychological Disorder

2020 ◽  
Vol 3 (4) ◽  
pp. 199-208
Author(s):  
Ambika Nand Jha ◽  
Dhaval M Patel
Keyword(s):  
Cannabinoid Receptors ◽  
Biological Effects ◽  
Endocannabinoid System ◽  
Brain Regions ◽  
The Body ◽  
Psychological Disorder ◽  
Physiological Processes ◽  
Neurochemical Changes ◽  
G Protein Coupled

Cannabinoid receptors, located throughout the body, are part of the endocannabinoid system. Cannabinoid CB1 and CB2 receptors are G protein-coupled receptors present from the early stages of gestation, which is involved in various physiological processes, including appetite, pain-sensation, mood, and memory. Due to the lipophilic nature of cannabinoids, it was initially thought that these compounds exert several biological effects by disrupting the cell membrane nonspecifically. Recent biochemical and behavioral findings have demonstrated that blockade of CB1 receptors engenders antidepressant-like neurochemical changes (increases in extracellular levels of monoamines in cortical but not subcortical brain regions) and behavioral effects consistent with antidepressant/antistress activity. We aim to define various roles of cannabinoid receptors in modulating signaling pathways and association with several pathophysiological conditions.

scholarly journals Endocannabinoid system and pain: an introduction

2013 ◽  
Vol 73 (1) ◽  
pp. 106-117 ◽  
Author(s):  
James J. Burston ◽  
Stephen G. Woodhams
Keyword(s):  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Therapeutic Potential ◽  
Endocannabinoid System ◽  
Clinical Work ◽  
Brain Regions ◽  
Ventrolateral Medulla ◽  
Cannabinoid Type 1 Receptor ◽  
Pain Pathway

The endocannabinoid (EC) system consists of two main receptors: cannabinoid type 1 receptor cannabinoid receptors are found in both the central nervous system (CNS) and periphery, whereas the cannabinoid type 2 receptor cannabinoid receptor is found principally in the immune system and to a lesser extent in the CNS. The EC family consists of two classes of well characterised ligands; the N-acyl ethanolamines, such as N-arachidonoyl ethanolamide or anandamide (AEA), and the monoacylglycerols, such as 2-arachidonoyl glycerol. The various synthetic and catabolic pathways for these enzymes have been (with the exception of AEA synthesis) elucidated. To date, much work has examined the role of EC in nociceptive processing and the potential of targeting the EC system to produce analgesia. Cannabinoid receptors and ligands are found at almost every level of the pain pathway from peripheral sites, such as peripheral nerves and immune cells, to central integration sites such as the spinal cord, and higher brain regions such as the periaqueductal grey and the rostral ventrolateral medulla associated with descending control of pain. EC have been shown to induce analgesia in preclinical models of acute nociception and chronic pain states. The purpose of this review is to critically evaluate the evidence for the role of EC in the pain pathway and the therapeutic potential of EC to produce analgesia. We also review the present clinical work conducted with EC, and examine whether targeting the EC system might offer a novel target for analgesics, and also potentially disease-modifying interventions for pathophysiological pain states.

scholarly journals Targeting Adenosine Receptors: A Potential Pharmacological Avenue for Acute and Chronic Pain

2020 ◽  
Vol 21 (22) ◽  
pp. 8710
Author(s):  
Fabrizio Vincenzi ◽  
Silvia Pasquini ◽  
Pier Andrea Borea ◽  
Katia Varani
Keyword(s):  
Chronic Pain ◽  
Adenosine Receptors ◽  
Therapeutic Potential ◽  
G Protein Coupled Receptors ◽  
Preclinical Studies ◽  
Allosteric Modulators ◽  
Antinociceptive Effects ◽  
Pain Regulation ◽  
G Protein Coupled

Adenosine is a purine nucleoside, responsible for the regulation of multiple physiological and pathological cellular and tissue functions by activation of four G protein-coupled receptors (GPCR), namely A1, A2A, A2B, and A3 adenosine receptors (ARs). In recent years, extensive progress has been made to elucidate the role of adenosine in pain regulation. Most of the antinociceptive effects of adenosine are dependent upon A1AR activation located at peripheral, spinal, and supraspinal sites. The role of A2AAR and A2BAR is more controversial since their activation has both pro- and anti-nociceptive effects. A3AR agonists are emerging as promising candidates for neuropathic pain. Although their therapeutic potential has been demonstrated in diverse preclinical studies, no AR ligands have so far reached the market. To date, novel pharmacological approaches such as adenosine regulating agents and allosteric modulators have been proposed to improve efficacy and limit side effects enhancing the effect of endogenous adenosine. This review aims to provide an overview of the therapeutic potential of ligands interacting with ARs and the adenosinergic system for the treatment of acute and chronic pain.

scholarly journals Urocortins in the mammalian endocrine system

2019 ◽  
Vol 61 (1) ◽  
Author(s):  
Caterina Squillacioti ◽  
Alessandra Pelagalli ◽  
Giovanna Liguori ◽  
Nicola Mirabella
Keyword(s):  
Endocrine Cells ◽  
Potential Role ◽  
Endocrine System ◽  
Reproductive Organs ◽  
G Protein Coupled Receptors ◽  
Main Role ◽  
G Protein Coupled

Abstract Urocortins (Ucns), peptides belonging to the corticotropin-releasing hormone (CRH) family, are classified into Ucn1, Ucn2, and Ucn3. They are involved in regulating several body functions by binding to two G protein-coupled receptors: receptor type 1 (CRHR1) and type 2 (CRHR2). In this review, we provide a historical overview of research on Ucns and their receptors in the mammalian endocrine system. Although the literature on the topic is limited, we focused our attention particularly on the main role of Ucns and their receptors in regulating the hypothalamic–pituitary–adrenal and thyroid axes, reproductive organs, pancreas, gastrointestinal tract, and other tissues characterized by “diffuse” endocrine cells in mammals. The prominent function of these peptides in health conditions led us to also hypothesize an action of Ucn agonists/antagonists in stress and in various diseases with its critical consequences on behavior and physiology. The potential role of the urocortinergic system is an intriguing topic that deserves further in-depth investigations to develop novel strategies for preventing stress-related conditions and treating endocrine diseases.

scholarly journals The Roles of GRKs in Hemostasis and Thrombosis

2020 ◽  
Vol 21 (15) ◽  
pp. 5345
Author(s):  
Xi Chen ◽  
Xuefei Zhao ◽  
Matthew Cooper ◽  
Peisong Ma
Keyword(s):  
Platelet Activation ◽  
Potential Role ◽  
Thrombus Formation ◽  
Feedback Regulation ◽  
Cerebrovascular Diseases ◽  
G Protein Coupled Receptors ◽  
Heart Attacks ◽  
Common Causes ◽  
G Protein Coupled

Along with cancer, cardiovascular and cerebrovascular diseases remain by far the most common causes of death. Heart attacks and strokes are diseases in which platelets play a role, through activation on ruptured plaques and subsequent thrombus formation. Most platelet agonists activate platelets via G protein-coupled receptors (GPCRs), which make these receptors ideal targets for many antiplatelet drugs. However, little is known about the mechanisms that provide feedback regulation on GPCRs to limit platelet activation. Emerging evidence from our group and others strongly suggests that GPCR kinases (GRKs) are critical negative regulators during platelet activation and thrombus formation. In this review, we will summarize recent findings on the role of GRKs in platelet biology and how one specific GRK, GRK6, regulates the hemostatic response to vascular injury. Furthermore, we will discuss the potential role of GRKs in thrombotic disorders, such as thrombotic events in COVID-19 patients. Studies on the function of GRKs during platelet activation and thrombus formation have just recently begun, and a better understanding of the role of GRKs in hemostasis and thrombosis will provide a fruitful avenue for understanding the hemostatic response to injury. It may also lead to new therapeutic options for the treatment of thrombotic and cardiovascular disorders.

scholarly journals A case of primary aldosteronism in pregnancy: do LH and GNRH receptors have a potential role in regulating aldosterone secretion?

2011 ◽  
Vol 164 (3) ◽  
pp. 405-412 ◽  
Author(s):  
N M Albiger ◽  
P Sartorato ◽  
B Mariniello ◽  
M Iacobone ◽  
I Finco ◽  
...  
Keyword(s):  
Primary Aldosteronism ◽  
Potential Role ◽  
Index Case ◽  
G Protein Coupled Receptors ◽  
Aldosterone Secretion ◽  
Normal Tissues ◽  
Gnrh Receptors ◽  
G Protein Coupled ◽  
In Pregnancy

ObjectiveThe mechanisms inducing steroidogenesis in primary aldosteronism (PA) remain poorly defined. It was recently demonstrated that some G-protein-coupled receptors are abnormally expressed in aldosterone-producing adenomas (APA). We evaluated the potential role of LH and GNRH receptors (LHR (or LHCGR) and GNRHR) in regulating aldosterone secretion in a patient with APA arising during pregnancy (index case) and in a subset of other patients with PA.Patients and methodsGNRH test was performed in the index case, 11 other PA, and 5 controls. GNRHR and LHR expressions were examined in 23 APA and 6 normal tissues.ResultsAldosterone response increased significantly (114%) in the index case after GNRH test was performed preoperatively, while it was blunted after adrenalectomy. Aldosterone also increased after human chorionic gonadotropin and triptorelin stimulation. A partial aldosterone response to GNRH was observed in other 7/11 PA, while a significant response was observed in two patients. Controls did not respond to GNRH test.GNRHR was overexpressed and LHR expression was moderate in the APA tissue from the index case. Moreover, LHR was found in normal adrenals and overexpressed in 6/22 APA. GNRHR was overexpressed in 6/22 APA, 2 of them with a 95- and 109-fold higher expression than normal. A correlation between the clinical and molecular findings was observed in five out of seven patients.ConclusionWe describe a case of PA diagnosed during pregnancy, which appeared to correlate with aberrant LHR and GNRHR expression. Our findings suggest that a subset of patients with PA has aberrant LHR and GNRHR expression, which could modulate aldosterone secretion.

scholarly journals Therapeutic Attributes of Endocannabinoid System against Neuro-Inflammatory Autoimmune Disorders

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3389
Author(s):  
Ishtiaq Ahmed ◽  
Saif Ur Rehman ◽  
Shiva Shahmohamadnejad ◽  
Muhammad Anjum Zia ◽  
Muhammad Ahmad ◽  
...  
Keyword(s):  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Therapeutic Potential ◽  
Endocannabinoid System ◽  
Cell Types ◽  
Autoimmune Disorders ◽  
Specific Receptors ◽  
Different Cell Types

In humans, various sites like cannabinoid receptors (CBR) having a binding affinity with cannabinoids are distributed on the surface of different cell types, where endocannabinoids (ECs) and derivatives of fatty acid can bind. The binding of these substance(s) triggers the activation of specific receptors required for various physiological functions, including pain sensation, memory, and appetite. The ECs and CBR perform multiple functions via the cannabinoid receptor 1 (CB1); cannabinoid receptor 2 (CB2), having a key effect in restraining neurotransmitters and the arrangement of cytokines. The role of cannabinoids in the immune system is illustrated because of their immunosuppressive characteristics. These characteristics include inhibition of leucocyte proliferation, T cells apoptosis, and induction of macrophages along with reduced pro-inflammatory cytokines secretion. The review seeks to discuss the functional relationship between the endocannabinoid system (ECS) and anti-tumor characteristics of cannabinoids in various cancers. The therapeutic potential of cannabinoids for cancer—both in vivo and in vitro clinical trials—has also been highlighted and reported to be effective in mice models in arthritis for the inflammation reduction, neuropathic pain, positive effect in multiple sclerosis and type-1 diabetes mellitus, and found beneficial for treating in various cancers. In human models, such studies are limited; thereby, further research is indispensable in this field to get a conclusive outcome. Therefore, in autoimmune disorders, therapeutic cannabinoids can serve as promising immunosuppressive and anti-fibrotic agents.

scholarly journals Positron Emission Tomography in the Inflamed Cerebellum: Addressing Novel Targets among G Protein-Coupled Receptors and Immune Receptors

Pharmaceutics ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 925
Author(s):  
Margit Pissarek
Keyword(s):  
G Protein ◽  
Cannabinoid Receptors ◽  
G Protein Coupled Receptors ◽  
Translocator Protein ◽  
Brain Diseases ◽  
Present Contribution ◽  
Binding Behavior ◽  
Positron Emission ◽  
Inflammatory Processes ◽  
G Protein Coupled

Inflammatory processes preceding clinical manifestation of brain diseases are moving increasingly into the focus of positron emission tomographic (PET) investigations. A key role in inflammation and as a target of PET imaging efforts is attributed to microglia. Cerebellar microglia, with a predominant ameboid and activated subtype, is of special interest also regarding improved and changing knowledge on functional involvement of the cerebellum in mental activities in addition to its regulatory role in motor function. The present contribution considers small molecule ligands as potential PET tools for the visualization of several receptors recognized to be overexpressed in microglia and which can potentially serve as indicators of inflammatory processes in the cerebellum. The sphingosine 1 phosphate receptor 1 (S1P1), neuropeptide Y receptor 2 (NPY2) and purinoceptor Y12 (P2Y12) cannabinoid receptors and the chemokine receptor CX3CR1 as G-protein-coupled receptors and the ionotropic purinoceptor P2X7 provide structures with rather classical binding behavior, while the immune receptor for advanced glycation end products (RAGE) and the triggering receptor expressed on myeloid cells 2 (TREM2) might depend for instance on further accessory proteins. Improvement in differentiation between microglial functional subtypes in comparison to the presently used 18 kDa translocator protein ligands as well as of the knowledge on the role of polymorphisms are special challenges in such developments.

Sign in / Sign up

Export Citation Format

Share Document