scholarly journals The Role of Leukotrienes as Potential Therapeutic Targets in Allergic Disorders

2019 ◽  
Vol 20 (14) ◽  
pp. 3580 ◽  
Author(s):  
Airi Jo-Watanabe ◽  
Toshiaki Okuno ◽  
Takehiko Yokomizo
Keyword(s):  
Biological Effects ◽  
Expression Patterns ◽  
Allergic Diseases ◽  
G Protein Coupled Receptors ◽  
Receptor Subtype ◽  
Recent Developments ◽  
Acute And Chronic Inflammation ◽  
Allergic Disorders ◽  
G Protein Coupled

Leukotrienes (LTs) are lipid mediators that play pivotal roles in acute and chronic inflammation and allergic diseases. They exert their biological effects by binding to specific G-protein-coupled receptors. Each LT receptor subtype exhibits unique functions and expression patterns. LTs play roles in various allergic diseases, including asthma (neutrophilic asthma and aspirin-sensitive asthma), allergic rhinitis, atopic dermatitis, allergic conjunctivitis, and anaphylaxis. This review summarizes the biology of LTs and their receptors, recent developments in the area of anti-LT strategies (in settings such as ongoing clinical studies), and prospects for future therapeutic applications.

scholarly journals Evaluation on Potential Contributions of Protease Activated Receptors Related Mediators in Allergic Inflammation

2014 ◽  
Vol 2014 ◽  
pp. 1-20 ◽  
Author(s):  
Huiyun Zhang ◽  
Xiaoning Zeng ◽  
Shaoheng He
Keyword(s):  
Serine Proteases ◽  
Inflammatory Cell ◽  
Allergic Inflammation ◽  
G Protein Coupled Receptors ◽  
Cell Behavior ◽  
Protease Activated Receptors ◽  
Pathologic Process ◽  
Allergic Disorders ◽  
G Protein Coupled

Protease activated receptors (PARs) have been recognized as a distinctive four-member family of seven transmembrane G protein-coupled receptors (GPCRs) that can be cleaved by certain serine proteases. In recent years, there has been considerable interest in the role of PARs in allergic inflammation, the fundamental pathologic changes of allergy, but the potential roles of PARs in allergy remain obscure. Since many of these proteases are produced and actively involved in the pathologic process of inflammation including exudation of plasma components, inflammatory cell infiltration, and tissue damage and repair, PARs appear to make important contribution to allergy. The aim of the present review is to summarize the expression of PARs in inflammatory and structural cells, the influence of agonists or antagonists of PARs on cell behavior, and the involvement of PARs in allergic disorders, which will help us to better understand the roles of serine proteases and PARs in allergy.

scholarly journals A neutrophil-centric view of chemotaxis

2019 ◽  
Vol 63 (5) ◽  
pp. 607-618 ◽  
Author(s):  
Melina Michael ◽  
Sonja Vermeren
Keyword(s):  
Chemokine Receptors ◽  
Neutrophil Migration ◽  
G Protein Coupled Receptors ◽  
Innate Immune ◽  
Resolution Of Inflammation ◽  
Neutrophil Extravasation ◽  
Recent Developments ◽  
G Protein Coupled

Abstract Neutrophils are key players of the innate immune system, that are involved in coordinating the initiation, propagation and resolution of inflammation. Accurate neutrophil migration (chemotaxis) to sites of inflammation in response to gradients of chemoattractants is pivotal to these roles. Binding of chemoattractants to dedicated G-protein-coupled receptors (GPCRs) initiates downstream signalling events that promote neutrophil polarisation, a prerequisite for directional migration. We provide a brief summary of some of the recent insights into signalling events and feedback loops that serve to initiate and maintain neutrophil polarisation. This is followed by a discussion of recent developments in the understanding of in vivo neutrophil chemotaxis, a process that is frequently referred to as ‘recruitment’ or ‘trafficking’. Here, we summarise neutrophil mobilisation from and homing to the bone marrow, and briefly discuss the role of glucosaminoglycan-immobilised chemoattractants and their corresponding receptors in the regulation of neutrophil extravasation and neutrophil swarming. We furthermore touch on some of the most recent insights into the roles of atypical chemokine receptors (ACKRs) in neutrophil recruitment, and discuss neutrophil reverse (transendothelial) migration together with potential function(s) in the dissemination and/or resolution of inflammation.

scholarly journals GRKs as Modulators of Neurotransmitter Receptors

Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 52
Author(s):  
Eugenia V. Gurevich ◽  
Vsevolod V. Gurevich
Keyword(s):  
G Protein ◽  
General Model ◽  
G Protein Coupled Receptors ◽  
Receptor Internalization ◽  
Neurotransmitter Receptors ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Receptor Kinase ◽  
G Protein Coupled ◽  
Homologous Desensitization

Many receptors for neurotransmitters, such as dopamine, norepinephrine, acetylcholine, and neuropeptides, belong to the superfamily of G protein-coupled receptors (GPCRs). A general model posits that GPCRs undergo two-step homologous desensitization: the active receptor is phosphorylated by kinases of the G protein-coupled receptor kinase (GRK) family, whereupon arrestin proteins specifically bind active phosphorylated receptors, shutting down G protein-mediated signaling, facilitating receptor internalization, and initiating distinct signaling pathways via arrestin-based scaffolding. Here, we review the mechanisms of GRK-dependent regulation of neurotransmitter receptors, focusing on the diverse modes of GRK-mediated phosphorylation of receptor subtypes. The immediate signaling consequences of GRK-mediated receptor phosphorylation, such as arrestin recruitment, desensitization, and internalization/resensitization, are equally diverse, depending not only on the receptor subtype but also on phosphorylation by GRKs of select receptor residues. We discuss the signaling outcome as well as the biological and behavioral consequences of the GRK-dependent phosphorylation of neurotransmitter receptors where known.

scholarly journals Role of Taste Receptors as Sentinels of Innate Immunity in the Upper Airway

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Neil N. Patel ◽  
Alan D. Workman ◽  
Noam A. Cohen
Keyword(s):  
Airway Epithelium ◽  
Taste Receptor ◽  
Upper Airway ◽  
Airway Disease ◽  
G Protein Coupled Receptors ◽  
Innate Immune ◽  
Taste Receptors ◽  
Taste Sensation ◽  
G Protein Coupled

Evidence is emerging that shows taste receptors serve functions outside of taste sensation of the tongue. Taste receptors have been found in tissue across the human body, including the gastrointestinal tract, bladder, brain, and airway. These extraoral taste receptors appear to be important in modulating the innate immune response through detection of pathogens. This review discusses taste receptor signaling, focusing on the G-protein–coupled receptors that detect bitter and sweet compounds in the upper airway epithelium. Emphasis is given to recent studies which link the physiology of sinonasal taste receptors to clinical manifestation of upper airway disease.

scholarly journals The Role of G Protein-Coupled Receptors in the Right Ventricle in Pulmonary Hypertension

2018 ◽  
Vol 5 ◽  
Author(s):  
Gayathri Viswanathan ◽  
Argen Mamazhakypov ◽  
Ralph T. Schermuly ◽  
Sudarshan Rajagopal
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricle ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
The Right ◽  
G Protein Coupled

scholarly journals Dopamine and GPCR-mediated modulation of DN1 clock neurons gates the circadian timing of sleep

2021 ◽  
Author(s):  
Matthias Schlichting ◽  
Shlesha Richhariya ◽  
Nicholas Herndon ◽  
Dingbang Ma ◽  
Jason Xin ◽  
...  
Keyword(s):  
G Protein Coupled Receptors ◽  
Sleep Regulation ◽  
Single Cell Sequencing ◽  
Sleep Timing ◽  
Clock Network ◽  
Sleep Centers ◽  
Neuron Synchronization ◽  
G Protein Coupled ◽  
Behavioral Screen

The metronome-like circadian regulation of sleep timing must still adapt to an uncertain environment. Recent studies in Drosophila indicate that neuromodulation not only plays a key role in clock neuron synchronization but also affects interactions between the clock network and brain sleep centers. We show here that the targets of neuromodulators, G-Protein Coupled Receptors (GPCRs), are highly enriched in the fly brain circadian clock network. Single cell sequencing indicates that they are not only differentially expressed but also define clock neuron identity. We generated a comprehensive guide library to mutagenize individual GPCRs in specific neurons and verified the strategy with a targeted sequencing approach. Combined with a behavioral screen, the mutagenesis strategy revealed a novel role of dopamine in sleep regulation by identifying two dopamine receptors and a clock neuron subpopulation that gate the timing of sleep.

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 The role of membrane curvature elastic stress for function of rhodopsin-like G protein-coupled receptors

Biochimie ◽  
2014 ◽  
Vol 107 ◽  
pp. 28-32 ◽  
Author(s):  
Olivier Soubias ◽  
Walter E. Teague ◽  
Kirk G. Hines ◽  
Klaus Gawrisch
Keyword(s):  
G Protein ◽  
Elastic Stress ◽  
Membrane Curvature ◽  
G Protein Coupled Receptors ◽  
G Protein Coupled

Immunology and allergy

2018 ◽  
pp. 333-380
Author(s):  
Drew Provan
Keyword(s):  
Immune Deficiency ◽  
Autoimmune Diseases ◽  
Serum Proteins ◽  
Allergic Diseases ◽  
Immunochemical Analysis ◽  
And Function ◽  
Allergic Disorders ◽  
Critical Results ◽  
Abnormal Results

This chapter covers the role of the immunology laboratory in the diagnosis of immunological and allergic disorders, including testing for autoimmune diseases, allergic diseases, lymphocyte and neutrophil phenotype and function, and immunochemical analysis of serum proteins for the diagnosis of immune deficiency and myeloma. Information is provided on the tests, with ranges and explanation of the interpretation of abnormal results. Critical results requiring immediate action are highlighted.

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