scholarly journals Eicosanoids

2020 ◽  
Vol 64 (3) ◽  
pp. 423-441 ◽  
Author(s):  
Philip C. Calder
Keyword(s):  
Nuclear Receptors ◽  
Cell Types ◽  
Vital Role ◽  
G Protein Coupled Receptors ◽  
Eicosanoid Synthesis ◽  
Reproductive Systems ◽  
Disease Treatment ◽  
G Protein Coupled ◽  
Derivatives Of ◽  
Physiological Systems

Abstract This article describes the pathways of eicosanoid synthesis, eicosanoid receptors, the action of eicosanoids in different physiological systems, the roles of eicosanoids in selected diseases, and the major inhibitors of eicosanoid synthesis and action. Eicosanoids are oxidised derivatives of 20-carbon polyunsaturated fatty acids (PUFAs) formed by the cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (cytP450) pathways. Arachidonic acid (ARA) is the usual substrate for eicosanoid synthesis. The COX pathways form prostaglandins (PGs) and thromboxanes (TXs), the LOX pathways form leukotrienes (LTs) and lipoxins (LXs), and the cytP450 pathways form various epoxy, hydroxy and dihydroxy derivatives. Eicosanoids are highly bioactive acting on many cell types through cell membrane G-protein coupled receptors, although some eicosanoids are also ligands for nuclear receptors. Because they are rapidly catabolised, eicosanoids mainly act locally to the site of their production. Many eicosanoids have multiple, sometimes pleiotropic, effects on inflammation and immunity. The most widely studied is PGE2. Many eicosanoids have roles in the regulation of the vascular, renal, gastrointestinal and female reproductive systems. Despite their vital role in physiology, eicosanoids are often associated with disease, including inflammatory disease and cancer. Inhibitors have been developed that interfere with the synthesis or action of various eicosanoids and some of these are used in disease treatment, especially for inflammation.

scholarly journals The Biology of Vasopressin

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 89
Author(s):  
Samantha Sparapani ◽  
Cassandra Millet-Boureima ◽  
Joshua Oliver ◽  
Kathy Mu ◽  
Pegah Hadavi ◽  
...  
Keyword(s):  
Parental Behavior ◽  
Cell Types ◽  
G Protein Coupled Receptors ◽  
Receptor Expression ◽  
Evolutionarily Conserved ◽  
Terrestrial Environments ◽  
Intracellular Vesicles ◽  
G Protein Coupled ◽  
Neuropsychiatric Conditions ◽  
Vasopressin Synthesis

Vasopressins are evolutionarily conserved peptide hormones. Mammalian vasopressin functions systemically as an antidiuretic and regulator of blood and cardiac flow essential for adapting to terrestrial environments. Moreover, vasopressin acts centrally as a neurohormone involved in social and parental behavior and stress response. Vasopressin synthesis in several cell types, storage in intracellular vesicles, and release in response to physiological stimuli are highly regulated and mediated by three distinct G protein coupled receptors. Other receptors may bind or cross-bind vasopressin. Vasopressin is regulated spatially and temporally through transcriptional and post-transcriptional mechanisms, sex, tissue, and cell-specific receptor expression. Anomalies of vasopressin signaling have been observed in polycystic kidney disease, chronic heart failure, and neuropsychiatric conditions. Growing knowledge of the central biological roles of vasopressin has enabled pharmacological advances to treat these conditions by targeting defective systemic or central pathways utilizing specific agonists and antagonists.

scholarly journals A Minimal Model for G Protein–Mediated Synaptic Facilitation and Depression

2003 ◽  
Vol 90 (3) ◽  
pp. 1643-1653 ◽  
Author(s):  
Richard Bertram ◽  
Jessica Swanson ◽  
Mohammad Yousef ◽  
Zhong-Ping Feng ◽  
Gerald W. Zamponi
Keyword(s):  
G Protein ◽  
Cell Types ◽  
G Protein Coupled Receptors ◽  
Β Subunit ◽  
Short Term ◽  
Paired Pulse ◽  
Synaptic Facilitation ◽  
Protein Inhibition ◽  
G Protein Coupled ◽  
High Pass

G protein–coupled receptors are ubiquitous in neurons, as well as other cell types. Activation of receptors by hormones or neurotransmitters splits the G protein heterotrimer into Gα and Gβγ subunits. It is now clear that Gβγ directly inhibits Ca2+ channels, putting them into a reluctant state. The effects of Gβγ depend on the specific β and γ subunits present, as well as the β subunit isoform of the N-type Ca2+ channel. We describe a minimal mathematical model for the effects of G protein action on the dynamics of synaptic transmission. The model is calibrated by data obtained by transfecting G protein and Ca2+ channel subunits into tsA-201 cells. We demonstrate with numerical simulations that G protein action can provide a mechanism for either short-term synaptic facilitation or depression, depending on the manner in which G protein–coupled receptors are activated. The G protein action performs high-pass filtering of the presynaptic signal, with a filter cutoff that depends on the combination of G protein and Ca2+ channel subunits present. At stimulus frequencies above the cutoff, trains of single spikes are transmitted, while only doublets are transmitted at frequencies below the cutoff. Finally, we demonstrate that relief of G protein inhibition can contribute to paired-pulse facilitation.

Compartmentalization of GPCR signalling controls unique cellular responses

2016 ◽  
Vol 44 (2) ◽  
pp. 562-567 ◽  
Author(s):  
Andrew M. Ellisdon ◽  
Michelle L. Halls
Keyword(s):  
Drug Discovery ◽  
Drug Targets ◽  
Cell Types ◽  
G Protein Coupled Receptors ◽  
Attrition Rates ◽  
Physiological Processes ◽  
Simple Chain ◽  
G Protein Coupled ◽  
Major Drug ◽  
Very High

With >800 members, G protein-coupled receptors (GPCRs) are the largest class of cell-surface signalling proteins, and their activation mediates diverse physiological processes. GPCRs are ubiquitously distributed across all cell types, involved in many diseases and are major drug targets. However, GPCR drug discovery is still characterized by very high attrition rates. New avenues for GPCR drug discovery may be provided by a recent shift away from the traditional view of signal transduction as a simple chain of events initiated from the plasma membrane. It is now apparent that GPCR signalling is restricted to highly organized compartments within the cell, and that GPCRs activate distinct signalling pathways once internalized. A high-resolution understanding of how compartmentalized signalling is controlled will probably provide unique opportunities to selectively and therapeutically target GPCRs.

ChemInform Abstract: Derivatives of (R)-1,11-Methyleneaporphine: Synthesis, Structure, and Interactions with G-Protein Coupled Receptors.

ChemInform ◽  
2010 ◽  
Vol 31 (28) ◽  
pp. no-no
Author(s):  
Tero Linnanen ◽  
Magnus Brisander ◽  
Lena Unelius ◽  
Goeran Sundholm ◽  
Uli Hacksell ◽  
...  
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptors ◽  
G Protein Coupled ◽  
Derivatives Of

scholarly journals Membrane progesterone receptor induces meiosis in Xenopus oocytes through endocytosis into signaling endosomes and interaction with APPL1 and Akt2

PLoS Biology ◽  
2020 ◽  
Vol 18 (11) ◽  
pp. e3000901
Author(s):  
Nancy Nader ◽  
Maya Dib ◽  
Rawad Hodeify ◽  
Raphael Courjaret ◽  
Asha Elmi ◽  
...  
Keyword(s):  
Nuclear Receptors ◽  
Xenopus Oocytes ◽  
Steroid Hormone ◽  
Adaptor Protein ◽  
G Protein Coupled Receptors ◽  
Adiponectin Receptors ◽  
Physiological Processes ◽  
Oocyte Meiosis ◽  
Membrane Progesterone Receptor ◽  
G Protein Coupled

The steroid hormone progesterone (P4) mediates many physiological processes through either nuclear receptors that modulate gene expression or membrane P4 receptors (mPRs) that mediate nongenomic signaling. mPR signaling remains poorly understood. Here we show that the topology of mPRβ is similar to adiponectin receptors and opposite to that of G-protein-coupled receptors (GPCRs). Using Xenopus oocyte meiosis as a well-established physiological readout of nongenomic P4 signaling, we demonstrate that mPRβ signaling requires the adaptor protein APPL1 and the kinase Akt2. We further show that P4 induces clathrin-dependent endocytosis of mPRβ into signaling endosome, where mPR interacts transiently with APPL1 and Akt2 to induce meiosis. Our findings outline the early steps involved in mPR signaling and expand the spectrum of mPR signaling through the multitude of pathways involving APPL1.

scholarly journals The Biology of Prostaglandins and Their Role as a Target for Allergic Airway Disease Therapy

2020 ◽  
Vol 21 (5) ◽  
pp. 1851 ◽  
Author(s):  
Kijeong Lee ◽  
Sang Hag Lee ◽  
Tae Hoon Kim
Keyword(s):  
Nasal Polyposis ◽  
Allergic Inflammation ◽  
Cell Types ◽  
Airway Disease ◽  
G Protein Coupled Receptors ◽  
Allergic Airway Disease ◽  
Airway Diseases ◽  
Disease Therapy ◽  
Lipid Compounds ◽  
G Protein Coupled

Prostaglandins (PGs) are a family of lipid compounds that are derived from arachidonic acid via the cyclooxygenase pathway, and consist of PGD2, PGI2, PGE2, PGF2, and thromboxane B2. PGs signal through G-protein coupled receptors, and individual PGs affect allergic inflammation through different mechanisms according to the receptors with which they are associated. In this review article, we have focused on the metabolism of the cyclooxygenase pathway, and the distinct biological effect of each PG type on various cell types involved in allergic airway diseases, including asthma, allergic rhinitis, nasal polyposis, and aspirin-exacerbated respiratory disease.

scholarly journals Lysophospholipids in the limelight

2002 ◽  
Vol 158 (2) ◽  
pp. 197-199 ◽  
Author(s):  
Wouter H. Moolenaar
Keyword(s):  
Growth Factor ◽  
Cell Motility ◽  
Tumor Progression ◽  
G Protein ◽  
Lysophosphatidic Acid ◽  
Cell Types ◽  
G Protein Coupled Receptors ◽  
Serum Phospholipid ◽  
A Cell ◽  
G Protein Coupled

Lysophosphatidic acid (LPA) is a serum phospholipid that evokes growth factor–like responses in many cell types through the activation of its G protein–coupled receptors. Although much is known about LPA signaling, it has remained unclear where and how bioactive LPA is produced. Umezu-Goto et al. (2002)(this issue, page 227) have purified a serum lysophospholipase D that generates LPA from lysophosphatidylcholine and found it to be identical to autotaxin, a cell motility–stimulating ectophosphodiesterase implicated in tumor progression. This result is surprising, as there was previously no indication that autotaxin could act as a phospholipase.

scholarly journals cAMP Signaling Regulates DNA Demethylation by Augmenting the Intracellular Labile Ferrous Iron Pool

2017 ◽  
Author(s):  
Vladimir Camarena ◽  
David W. Sant ◽  
Tyler C. Huff ◽  
Sushmita Mustafi ◽  
Ryan K. Muir ◽  
...  
Keyword(s):  
Gene Transcription ◽  
Phosphodiesterase Inhibitors ◽  
Cell Types ◽  
Dna Demethylation ◽  
G Protein Coupled Receptors ◽  
Camp Signaling ◽  
Multiple Cell ◽  
Iron Pool ◽  
Transcriptomic Changes ◽  
G Protein Coupled

AbstractIt is widely accepted that cAMP regulates gene transcription principally by activating the protein kinase A (PKA)-targeted transcription factors. Here, we show that cAMP enhances the generation of 5-hydroxymethylcytosine (5hmC) in multiple cell types. 5hmC is converted from 5-methylcytosine (5mC) by Tet methylcytosine dioxygenases, for which Fe(II) is an essential cofactor. The promotion of 5hmC was mediated by a prompt increase of the intracellular labile Fe(II) pool (LIP). cAMP enhanced the acidification of endosomes for Fe(II) release to the LIP likely through RapGEF2. The effect of cAMP on Fe(II) and 5hmC was confirmed by adenylate cyclase activators, phosphodiesterase inhibitors, and most notably by stimulation of G protein-coupled receptors (GPCR). The transcriptomic changes caused by cAMP occurred in concert with 5hmC elevation in differentially transcribed genes. Collectively, these data show a previously unrecognized regulation of gene transcription by GPCR-cAMP signaling through augmentation of the intracellular labile Fe(II) pool and DNA demethylation.

scholarly journals Signal Transduction of Sphingosine-1-Phosphate G Protein—Coupled Receptors

2006 ◽  
Vol 6 ◽  
pp. 946-966 ◽  
Author(s):  
Nicholas Young ◽  
James R. Van Brocklyn
Keyword(s):  
Signal Transduction ◽  
G Protein ◽  
Cell Types ◽  
G Protein Coupled Receptors ◽  
Lymphocyte Trafficking ◽  
Cytoskeletal Organization ◽  
Cellular Effects ◽  
Sphingosine 1 Phosphate ◽  
S1p Receptor ◽  
G Protein Coupled

Sphingosine-1-phosphate (S1P) is a bioactive lipid capable of eliciting dramatic effects in a variety of cell types. Signaling by this molecule is by a family of five G protein—coupled receptors named S1P1–5that signal through a variety of pathways to regulate cell proliferation, migration, cytoskeletal organization, and differentiation. These receptors are expressed in a wide variety of tissues and cell types, and their cellular effects contribute to important biological and pathological functions of S1P in many processes, including angiogenesis, vascular development, lymphocyte trafficking, and cancer. This review will focus on the current progress in the field of S1P receptor signaling and biology.

Derivatives of (R)-1,11-Methyleneaporphine:  Synthesis, Structure, and Interactions with G-Protein Coupled Receptors

2000 ◽  
Vol 43 (7) ◽  
pp. 1339-1349 ◽  
Author(s):  
Tero Linnanen ◽  
Magnus Brisander ◽  
Lena Unelius ◽  
Göran Sundholm ◽  
Uli Hacksell ◽  
...  
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptors ◽  
G Protein Coupled ◽  
Derivatives Of
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