scholarly journals The Role of Apelin/Apelin Receptor in Energy Metabolism and Water Homeostasis: A Comprehensive Narrative Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Gonghui Hu ◽  
Zhen Wang ◽  
Rumin Zhang ◽  
Wenping Sun ◽  
Xiaoyu Chen
Keyword(s):  
Energy Metabolism ◽  
Cardiac Contractility ◽  
Water Excretion ◽  
Water Homeostasis ◽  
The Family ◽  
The Central Nervous System ◽  
Apelin Receptor ◽  
Clinical Drugs ◽  
G Protein Coupled

The apelin receptor (APJ) is a member of the family A of G-protein-coupled receptors (GPCRs) and is involved in range of physiological and pathological functions, including fluid homeostasis, anxiety, and depression, as well as cardiovascular and metabolic disorders. APJ was classically described as a monomeric transmembrane receptor that forms a ternary complex together with its ligand and associated G proteins. More recently, increasing evidence indicates that APJ may interact with other GPCRs to form heterodimers, which may selectively modulate distinct intracellular signal transduction pathways. Besides, the apelin/APJ system plays important roles in the physiology and pathophysiology of several organs, including regulation of blood pressure, cardiac contractility, angiogenesis, metabolic balance, and cell proliferation, apoptosis, or inflammation. Additionally, the apelin/APJ system is widely expressed in the central nervous system, especially in neurons and oligodendrocytes. This article reviews the role of apelin/APJ in energy metabolism and water homeostasis. Compared with the traditional diuretics, apelin exerts a positive inotropic effect on the heart, while increases water excretion. Therefore, drugs targeting apelin/APJ system undoubtedly provide more therapeutic options for patients with congestive heart failure accompanied with hyponatremia. To provide more precise guidance for the development of clinical drugs, further in-depth studies are warranted on the metabolism and signaling pathways associated with apelin/APJ system.

scholarly journals Shedding light on the role of CX3CR1 in the pathogenesis of schizophrenia

2021 ◽  
Author(s):  
Katarzyna Chamera ◽  
Magdalena Szuster-Głuszczak ◽  
Agnieszka Basta-Kaim
Keyword(s):  
Experimental Studies ◽  
Physiological Processes ◽  
Unique System ◽  
The Family ◽  
Inflammatory Processes ◽  
The Central Nervous System ◽  
G Protein Coupled ◽  
The Brain ◽  
Brain Homeostasis

AbstractSchizophrenia has a complex and heterogeneous molecular and clinical picture. Over the years of research on this disease, many factors have been suggested to contribute to its pathogenesis. Recently, the inflammatory processes have gained particular interest in the context of schizophrenia due to the increasing evidence from epidemiological, clinical and experimental studies. Within the immunological component, special attention has been brought to chemokines and their receptors. Among them, CX3C chemokine receptor 1 (CX3CR1), which belongs to the family of seven-transmembrane G protein-coupled receptors, and its cognate ligand (CX3CL1) constitute a unique system in the central nervous system. In the view of regulation of the brain homeostasis through immune response, as well as control of microglia reactivity, the CX3CL1–CX3CR1 system may represent an attractive target for further research and schizophrenia treatment. In the review, we described the general characteristics of the CX3CL1–CX3CR1 axis and the involvement of this signaling pathway in the physiological processes whose disruptions are reported to participate in mechanisms underlying schizophrenia. Furthermore, based on the available clinical and experimental data, we presented a guide to understanding the implication of the CX3CL1–CX3CR1 dysfunctions in the course of schizophrenia.

scholarly journals The Role of Prokineticin 2 in Oxidative Stress and in Neuropathological Processes

2021 ◽  
Vol 12 ◽  
Author(s):  
Roberta Lattanzi ◽  
Cinzia Severini ◽  
Daniela Maftei ◽  
Luciano Saso ◽  
Aldo Badiani
Keyword(s):  
Pain Perception ◽  
G Protein Coupled Receptors ◽  
Cellular Processes ◽  
Prokineticin 2 ◽  
Physiological Processes ◽  
Pathological Conditions ◽  
Double Function ◽  
The Central Nervous System ◽  
G Protein Coupled

The prokineticin (PK) family, prokineticin 1 and Bv8/prokineticin 2 (PROK2), initially discovered as regulators of gastrointestinal motility, interacts with two G protein-coupled receptors, PKR1 and PKR2, regulating important biological functions such as circadian rhythms, metabolism, angiogenesis, neurogenesis, muscle contractility, hematopoiesis, immune response, reproduction and pain perception. PROK2 and PK receptors, in particular PKR2, are widespread distributed in the central nervous system, in both neurons and glial cells. The PROK2 expression levels can be increased by a series of pathological insults, such as hypoxia, reactive oxygen species, beta amyloid and excitotoxic glutamate. This suggests that the PK system, participating in different cellular processes that cause neuronal death, can be a key mediator in neurological/neurodegenerative diseases. While many PROK2/PKRs effects in physiological processes have been documented, their role in neuropathological conditions is not fully clarified, since PROK2 can have a double function in the mechanisms underlying to neurodegeneration or neuroprotection. Here, we briefly outline the latest findings on the modulation of PROK2 and its cognate receptors following different pathological insults, providing information about their opposite neurotoxic and neuroprotective role in different pathological conditions.

scholarly journals Data Supporting a New Physiological Role for Brain Apelin in the Regulation of Hypothalamic Oxytocin Neurons in Lactating Rats

Endocrinology ◽  
2011 ◽  
Vol 152 (9) ◽  
pp. 3492-3503 ◽  
Author(s):  
Laurence Bodineau ◽  
Christopher Taveau ◽  
Hong-Hanh Lê Quan Sang ◽  
Guillaume Osterstock ◽  
Isabelle Queguiner ◽  
...  
Keyword(s):  
Direct Action ◽  
Physiological Role ◽  
Double Immunofluorescence ◽  
Endogenous Ligand ◽  
Electrophysiological Measurements ◽  
Apelin Receptor ◽  
Immunofluorescence Labeling ◽  
G Protein Coupled

Apelin is a bioactive peptide identified as the endogenous ligand of the human orphan G protein-coupled receptor APJ in 1998. The present data show that apelin modulates the activity of magnocellular and parvocellular oxytocin (OXY) neurons in the lactating rat. A combination of in situ hybridization and immunohistochemistry demonstrated the presence of apelin receptor mRNA in hypothalamic OXY neurons. Double immunofluorescence labeling then revealed the colocalization of apelin with OXY in about 20% of the hypothalamic OXY-positive neurons. Intracerebroventricular apelin administration inhibited the activity of magnocellular and parvocellular OXY neurons, as shown by measuring the c-fos expression in OXY neurons or by direct electrophysiological measurements of the electrical activity of these neurons. This effect was correlated with a decrease in the amount of milk ejected. Thus, apelin inhibits the activity of OXY neurons through a direct action on apelin receptors expressed by these neurons in an autocrine and paracrine manner. In conclusion, these findings highlight the inhibitory role of apelin as an autocrine/paracrine peptide acting on OXY neurons during breastfeeding.

Tissue specificity and physiological relevance of various isoforms of adenylyl cyclase

2000 ◽  
Vol 279 (3) ◽  
pp. F400-F416 ◽  
Author(s):  
Nicole Defer ◽  
Martin Best-Belpomme ◽  
Jacques Hanoune
Keyword(s):  
Adenylyl Cyclase ◽  
Inhibitory Effect ◽  
Relative Level ◽  
Extracellular Signals ◽  
Physiological Relevance ◽  
A Cell ◽  
The Central Nervous System ◽  
Cellular Transfection ◽  
G Protein Coupled

The present review focuses on the potential physiological regulations involving different isoforms of adenylyl cyclase (AC), the enzymatic activity responsible for the synthesis of cAMP from ATP. Depending on the properties and the relative level of the isoforms expressed in a tissue or a cell type at a specific time, extracellular signals received by the G protein-coupled receptors can be differently integrated. We report here on various aspects of such regulations, emphasizing the role of Ca2+/calmodulin in activating AC1 and AC8 in the central nervous system, the potential inhibitory effect of Ca2+ on AC5 and AC6, and the changes in the expression pattern of the isoforms during development. A particular emphasis is given to the role of cAMP during drug dependence. Present experimental limitations are also underlined (pitfalls in the interpretation of cellular transfection, scarcity of the invalidation models, and so on).

scholarly journals The Contribution of Formyl Peptide Receptor Dysfunction to the Course of Neuroinflammation: A Potential Role in the Brain Pathology

2020 ◽  
Vol 18 (3) ◽  
pp. 229-249 ◽  
Author(s):  
Ewa Trojan ◽  
Natalia Bryniarska ◽  
Monika Leśkiewicz ◽  
Magdalena Regulska ◽  
Katarzyna Chamera ◽  
...  
Keyword(s):  
Potential Role ◽  
Membrane Receptors ◽  
Formyl Peptide Receptor ◽  
Proinflammatory Response ◽  
Formyl Peptide ◽  
Inflammatory Processes ◽  
The Central Nervous System ◽  
G Protein Coupled ◽  
The Brain

: Chronic inflammatory processes within the central nervous system (CNS) are in part responsible for the development of neurodegenerative and psychiatric diseases. These processes are associated with, among other things, the increased and disturbed activation of microglia and the elevated production of proinflammatory factors. Recent studies indicated that the disruption of the process of resolution of inflammation (RoI) may be the cause of CNS disorders. It is shown that the RoI is regulated by endogenous molecules called specialized pro-resolving mediators (SPMs), which interact with specific membrane receptors. Some SPMs activate formyl peptide receptors (FPRs), which belong to the family of seven-transmembrane G protein-coupled receptors. These receptors take part not only in the proinflammatory response but also in the resolution of the inflammation process. Therefore, the activation of FPRs might have complex consequences. : This review discusses the potential role of FPRs, and in particular the role of FPR2 subtype, in the brain under physiological and pathological conditions and their involvement in processes underlying neurodegenerative and psychiatric disorders as well as ischemia, the pathogenesis of which involves the dysfunction of inflammatory processes.

scholarly journals Generation and Characterization of Rgs4 Mutant Mice

2005 ◽  
Vol 25 (10) ◽  
pp. 4221-4228 ◽  
Author(s):  
Nicolas Grillet ◽  
Alexandre Pattyn ◽  
Candice Contet ◽  
Brigitte L. Kieffer ◽  
Christo Goridis ◽  
...  
Keyword(s):  
Neural Development ◽  
Susceptibility Gene ◽  
Rgs Proteins ◽  
Biological Phenomena ◽  
The Central Nervous System ◽  
Discrete Populations ◽  
G Protein Coupled

ABSTRACT RGS proteins are negative regulators of signaling through heterotrimeric G protein-coupled receptors and, as such, are in a position to regulate a plethora of biological phenomena. However, those have just begun to be explored in vivo. Here, we describe a mouse line deficient for Rgs4, a gene normally expressed early on in discrete populations of differentiating neurons and later on at multiple sites of the central nervous system, the cortex in particular, where it is one of the most highly transcribed Rgs genes. Rgs4 lacZ/lacZ mice had normal neural development and were viable and fertile. Behavioral testing on mutant adults revealed subtle sensorimotor deficits but, so far, supported neither the proposed status of Rgs4 as a schizophrenia susceptibility gene (by showing intact prepulse inhibition in the mutants) nor (unlike another member of the Rgs family, Rgs9) a role of Rgs4 in the acute or chronic response to opioids.

scholarly journals Effects of a Novel GPR55 Antagonist on the Arachidonic Acid Cascade in LPS-Activated Primary Microglial Cells

2021 ◽  
Vol 22 (5) ◽  
pp. 2503
Author(s):  
Soraya Wilke Saliba ◽  
Franziska Gläser ◽  
Anke Deckers ◽  
Albrecht Keil ◽  
Thomas Hurrle ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Therapeutic Option ◽  
The Novel ◽  
Cns Disorders ◽  
Chronic Neuroinflammation ◽  
The Central Nervous System ◽  
Cox 2 ◽  
G Protein Coupled ◽  
Cox 1

Neuroinflammation is a crucial process to maintain homeostasis in the central nervous system (CNS). However, chronic neuroinflammation is detrimental, and it is described in the pathogenesis of CNS disorders, including Alzheimer’s disease (AD) and depression. This process is characterized by the activation of immune cells, mainly microglia. The role of the orphan G-protein-coupled receptor 55 (GPR55) in inflammation has been reported in different models. However, its role in neuroinflammation in respect to the arachidonic acid (AA) cascade in activated microglia is still lacking of comprehension. Therefore, we synthesized a novel GPR55 antagonist (KIT 10, 0.1–25 µM) and tested its effects on the AA cascade in lipopolysaccharide (LPS, 10 ng / mL)-treated primary rat microglia using Western blot and EIAs. We show here that KIT 10 potently prevented the release of prostaglandin E2 (PGE2), reduced microsomal PGE2 synthase (mPGES-1) and cyclooxygenase-2 (COX-2) synthesis, and inhibited the phosphorylation of Ikappa B-alpha (IκB-α), a crucial upstream step of the inflammation-related nuclear factor-kappaB (NF-κB) signaling pathway. However, no effects were observed on COX-1 and -2 activities and mitogen-activated kinases (MAPK). In summary, the novel GPR55 receptor antagonist KIT 10 reduces neuroinflammatory parameters in microglia by inhibiting the COX-2/PGE2 pathway. Further experiments are necessary to better elucidate its effects and mechanisms. Nevertheless, the modulation of inflammation by GPR55 might be a new therapeutic option to treat CNS disorders with a neuroinflammatory background such as AD or depression.

scholarly journals Endocannabinoid-Like Lipid Neuromodulators in the Regulation of Dopamine Signaling: Relevance for Drug Addiction

2020 ◽  
Vol 12 ◽  
Author(s):  
Claudia Sagheddu ◽  
Larissa Helena Torres ◽  
Tania Marcourakis ◽  
Marco Pistis
Keyword(s):  
Psychiatric Disorders ◽  
Biological Activities ◽  
Signaling System ◽  
Physiological Processes ◽  
Naturally Occurring ◽  
The Family ◽  
Complex Lipid ◽  
The Central Nervous System ◽  
Dopamine Signaling

The family of lipid neuromodulators has been rapidly growing, as the use of different -omics techniques led to the discovery of a large number of naturally occurring N-acylethanolamines (NAEs) and N-acyl amino acids belonging to the complex lipid signaling system termed endocannabinoidome. These molecules exert a variety of biological activities in the central nervous system, as they modulate physiological processes in neurons and glial cells and are involved in the pathophysiology of neurological and psychiatric disorders. Their effects on dopamine cells have attracted attention, as dysfunctions of dopamine systems characterize a range of psychiatric disorders, i.e., schizophrenia and substance use disorders (SUD). While canonical endocannabinoids are known to regulate excitatory and inhibitory synaptic inputs impinging on dopamine cells and modulate several dopamine-mediated behaviors, such as reward and addiction, the effects of other lipid neuromodulators are far less clear. Here, we review the emerging role of endocannabinoid-like neuromodulators in dopamine signaling, with a focus on non-cannabinoid N-acylethanolamines and their receptors. Mounting evidence suggests that these neuromodulators contribute to modulate synaptic transmission in dopamine regions and might represent a target for novel medications in alcohol and nicotine use disorder.

scholarly journals Size-selective opening of the blood–brain barrier by targeting endothelial sphingosine 1–phosphate receptor 1

2017 ◽  
Vol 114 (17) ◽  
pp. 4531-4536 ◽  
Author(s):  
Keisuke Yanagida ◽  
Catherine H. Liu ◽  
Giuseppe Faraco ◽  
Sylvain Galvani ◽  
Helen K. Smith ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Brain Inflammation ◽  
Brain Barrier ◽  
The Novel ◽  
Object Recognition Test ◽  
Blood Brain ◽  
Sphingosine 1 Phosphate ◽  
The Central Nervous System ◽  
G Protein Coupled

The vasculature of the central nervous system (CNS) forms a selective barrier termed the blood–brain barrier (BBB). Disruption of the BBB may contribute to various CNS diseases. Conversely, the intact BBB restricts efficient penetration of CNS-targeted drugs. Here, we report the BBB-regulatory role of endothelial sphingosine 1–phosphate (S1P) receptor-1, a G protein-coupled receptor known to promote the barrier function in peripheral vessels. Endothelial-specific S1pr1 knockout mice (S1pr1iECKO) showed BBB breach for small-molecular-mass fluorescence tracers (<3 kDa), but not larger tracers (>10 kDa). Chronic BBB leakiness was associated with cognitive impairment, as assessed by the novel object recognition test, but not signs of brain inflammation. Brain microvessels of S1pr1iECKO mice showed altered subcellular distribution of tight junctional proteins. Pharmacological inhibition of S1P1 function led to transient BBB breach. These data suggest that brain endothelial S1P1 maintain the BBB by regulating the proper localization of tight junction proteins and raise the possibility that endothelial S1P1 inhibition may be a strategy for transient BBB opening and delivery of small molecules into the CNS.

scholarly journals Role of GPR39 in Neurovascular Homeostasis and Disease

2021 ◽  
Vol 22 (15) ◽  
pp. 8200
Author(s):  
Yifan Xu ◽  
Anthony P. Barnes ◽  
Nabil J. Alkayed
Keyword(s):  
Central Nervous System ◽  
Immune Response ◽  
Vascular Tone ◽  
Neuronal Excitability ◽  
G Protein Coupled Receptors ◽  
Constitutive Activity ◽  
Biased Signaling ◽  
The Central Nervous System ◽  
G Protein Coupled

GPR39, a member of the ghrelin family of G protein-coupled receptors, is zinc-responsive and contributes to the regulation of diverse neurovascular and neurologic functions. Accumulating evidence suggests a role as a homeostatic regulator of neuronal excitability, vascular tone, and the immune response. We review GPR39 structure, function, and signaling, including constitutive activity and biased signaling, and summarize its expression pattern in the central nervous system. We further discuss its recognized role in neurovascular, neurological, and neuropsychiatric disorders.

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