scholarly journals AMP010014A09 in Sus Scrofa Encodes an Analog of G Protein-Coupled Receptor 109A, Which Mediates the Anti-Inflammatory Effects of Beta-Hydroxybutyric Acid

2017 ◽  
Vol 42 (4) ◽  
pp. 1420-1430 ◽  
Author(s):  
Guangxin Chen ◽  
Shoupeng Fu ◽  
Wenqian Feng ◽  
Bingxu Huang ◽  
Shiyao Xu ◽  
...  
Keyword(s):  
G Protein ◽  
Inflammatory Cytokines ◽  
Sus Scrofa ◽  
Hydroxybutyric Acid ◽  
G Protein Coupled Receptor ◽  
Anti Inflammatory ◽  
High Level ◽  
G Protein Coupled ◽  
Camp Levels ◽  
Pro Inflammatory Cytokines

Background: Hydroxy-carboxylic acid receptor 2 (HCA2, also called GPR109A) belongs to the G protein-coupled receptor (GPCR) family and is found in humans, rats, mice, hamsters and guinea pigs, but there are almost no reports of this protein in other species. In this investigation, we speculated that AMP010014A09 (AMP+) is a homologue of GPR109A in swine. Methods: To test this hypothesis, the following experiments were designed: monocytes isolated from the peripheral blood of swine were treated with LPS after pretreating with or without β-hydroxybutyric acid (BHBA), and the levels of pro-inflammatory cytokines and inflammatory proteins were assessed. cAMP levels induced by Forskolin in swine testicular (ST) and IPEC-J2 cells were detected with or without BHBA treatment and following silencing or stable transfection of the AMP+ gene. Results: AMP+ in swine exhibited a high level of homology with HM74A in humans and PUMA-G in mice. BHBA inhibited the LPS-induced secretion of the pro-inflammatory cytokines TNF-α, IL-6 and IL-1β and the inflammatory protein COX-2 in monocytes of swine. BHBA suppressed the Forskolin-induced cAMP level increase in ST cells, but failed to inhibit the accumulation of cAMP after the AMP+ gene was silenced with shRNA by transfecting cells with the pGPU6-GFP-Neo-AMP+-sus-392 plasmid. BHBA had no effect on cAMP levels in IPEC-J2 cells, but significantly inhibited the increase in cAMP induced by Forskolin treatment following transfection of the AMP+ gene into IPEC-J2 cells by a lentivirus vector. Conclusion: Our results indicated that AMP+ encodes a G protein-coupled receptor in Sus scrofa that inhibits cAMP levels and mediates anti-inflammatory effects in swine monocytes.

scholarly journals The Controversial C5a Receptor C5aR2: Its Role in Health and Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Ting Zhang ◽  
Malgorzata A. Garstka ◽  
Ke Li
Keyword(s):  
Animal Models ◽  
G Protein ◽  
Cellular Localization ◽  
G Protein Coupled Receptor ◽  
C5a Receptor ◽  
Intracellular Signals ◽  
Health And Disease ◽  
Anti Inflammatory ◽  
G Protein Coupled

After the discovery of the C5a receptor C5aR1, C5aR2 is the second receptor found to bind C5a and its des-arginine form. As a heptahelical G protein-coupled receptor but devoid of the intracellular Gα signal, C5aR2 is special and confusing. Ramifications and controversies about C5aR2 are under debate since its identification, from putative ligands and cellular localization to intracellular signals and pathological roles in inflammation and immunity. The ruleless and even conflicting pro- or anti-inflammatory role of C5aR2 in animal models of diverse diseases makes one bewildered. This review summarizes reports on C5aR2, tries to clear up available evidence on these four controversial aspects, and delineates C5aR2 function(s). It also summarizes available toolboxes for C5aR2 study.

scholarly journals The Habenular Receptor GPR151 Regulates Addiction Vulnerability Across Drug Classes

2019 ◽  
Author(s):  
Beatriz Antolin-Fontes ◽  
Kun Li ◽  
Jessica L. Ables ◽  
Michael H. Riad ◽  
Andreas Görlich ◽  
...  
Keyword(s):  
G Protein ◽  
Cannabinoid Receptors ◽  
Behavioral Responses ◽  
G Protein Coupled Receptor ◽  
Inhibitory Protein ◽  
Vesicle Release ◽  
Release Probability ◽  
Drug Classes ◽  
G Protein Coupled ◽  
Camp Levels

SUMMARYThe habenula controls the addictive properties of nicotine but also densely expresses opioid and cannabinoid receptors. As such, identification of strategies to manipulate habenular activity may yield new approaches to treat substance use disorders. Here we show that GPR151, an orphan G protein-coupled receptor (GPCR) highly enriched in the habenula of humans and rodents plays a critical role in regulating habenular function and behavioral responses to addictive drugs. We show that GPR151 is expressed on axonal and presynaptic membranes and synaptic vesicles, and regulates synaptic fidelity and plasticity. We find that GPR151 associates with synaptic components controlling vesicle release and ion transport and couples to the G-alpha inhibitory protein Gαo1to reduce cAMP levels. Stable cell lines expressing GPR151 confirm that it signals via Gi/o and are amenable to ligand screens.Gpr151null mice show diminished behavioral responses to nicotine, and self-administer greater quantities of the drug, phenotypes rescued by viral re-expression ofGpr151in the habenula.Gpr151null mice are also insensitive to the behavioral actions of morphine and cannabinoids. These data identify GPR151 as a critical modulator of habenular function that controls addiction vulnerability across different drug classes.HighlightsHabenula neurons are enriched in nicotinic, opioid, cannabinoid and GPR151 receptorsGPR151 modulates synaptic fidelity and release probability at habenular terminals.Habenular GPR151 plays a role in drug abuse and food intake/weight controlGPR151 couples to the G-alpha inhibitory protein Gαo1to reduce cAMP levels.eTOC BlurbAntolin-Fontes at al. identify a G protein-coupled receptor, GPR151, which is highly enriched in human habenular neurons. These neurons are primarily enriched with nicotinic, opioid and cannabinoid receptors. We find that GPR151 modulates habenular synaptic vesicle release probability and behavioral responses to these drugs of abuse.

Lysophosphatidylinositol, an Endogenous Ligand for G Protein-Coupled Receptor 55, Has Anti-inflammatory Effects in Cultured Microglia

Inflammation ◽  
2020 ◽  
Vol 43 (5) ◽  
pp. 1971-1987
Author(s):  
Tomoki Minamihata ◽  
Katsura Takano ◽  
Mitsuaki Moriyama ◽  
Yoichi Nakamura
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptor ◽  
Endogenous Ligand ◽  
Anti Inflammatory ◽  
G Protein Coupled

scholarly journals A Novel High Throughput Chemiluminescent Assay for the Measurement of Cellular Cyclic Adenosine Monophosphate Levels

2000 ◽  
Vol 5 (4) ◽  
pp. 239-247 ◽  
Author(s):  
Anthony C. Chiulli ◽  
Karen Trompeter ◽  
Michelle Palmer
Keyword(s):  
G Protein ◽  
High Throughput ◽  
High Throughput Screening ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Receptor Activation ◽  
G Protein Coupled Receptor ◽  
Wide Range ◽  
G Protein Coupled ◽  
Camp Levels

The second messenger 3′, 5′-cyclic AMP (cAMP) is a highly regulated molecule that is governed by G protein-coupled receptor activation and other cellular processes. Measurement of cAMP levels in cells is widely used as an indicator of receptor function in drug discovery applications. We have developed a nonradioactive ELISA for the accurate quantitation of cAMP levels produced in cell-based assays. This novel competitive assay utilizes chemiluminescent detection that affords both a sensitivity and a dynamic assay range that have not been previously reported with any other assay methodologies. The assay has been automated in 96- and 384-well formats, providing assay data that are equivalent to, if not better than, data generated by hand. This report demonstrates the application of this novel assay technology to the functional analysis of a specific G protein-coupled receptor, neuropeptide receptor Y1, on SK-N-MC cells. Our data indicate the feasibility of utilizing this assay methodology for monitoring cAMP levels in a wide range of functional cell-based assays for high throughput screening.

G protein-coupled receptor 39 plays an anti-inflammatory role by enhancing IL-10 production from macrophages under inflammatory conditions

2018 ◽  
Vol 834 ◽  
pp. 240-245 ◽  
Author(s):  
Satoshi Muneoka ◽  
Megumi Goto ◽  
Kumiko Kadoshima-Yamaoka ◽  
Reiko Kamei ◽  
Maki Terakawa ◽  
...  
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptor ◽  
Inflammatory Conditions ◽  
Anti Inflammatory ◽  
G Protein Coupled

scholarly journals Cardioprotective and anti-inflammatory effects of G-protein coupled receptor 30 (GPR30) on postmenopausal type 2 diabetic rats

2018 ◽  
Vol 108 ◽  
pp. 153-164 ◽  
Author(s):  
Hossein Azizian ◽  
Mohammad Khaksari ◽  
Gholamreza Asadi karam ◽  
Mansour Esmailidehaj ◽  
Zeinab Farhadi
Keyword(s):  
G Protein ◽  
Diabetic Rats ◽  
G Protein Coupled Receptor ◽  
Anti Inflammatory ◽  
G Protein Coupled ◽  
Type 2 Diabetic

scholarly journals Studies of involvement of G-protein coupled receptor-3 in cannabidiol effects on inflammatory responses of mouse primary astrocytes and microglia

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0251677
Author(s):  
Jun Wu ◽  
Nu Chen ◽  
Yongqing Liu ◽  
Grzegorz Godlewski ◽  
Henry J. Kaplan ◽  
...  
Keyword(s):  
G Protein ◽  
Glial Cells ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
G Protein Coupled Receptor ◽  
Primary Astrocytes ◽  
Anti Inflammatory ◽  
G Protein Coupled

Cannabidiol (CBD) exhibits anti-inflammatory and neuroprotective properties and is suggested to be effective in the pre-clinical and clinical treatment of illnesses of the central nervous system (CNS). Two major types of CNS glial cells, astrocytes and microglia, play critical roles in the development and pathogenesis of CNS diseases. However, the mechanisms by which CBD plays an anti-inflammatory and neuroprotective role for these glial cells have not been fully elucidated. In this study, we examined the effects of CBD on the inflammatory response of mouse primary astrocytes and microglia. We also investigated whether the effect of CBD on cytokine release is mediated by the G protein coupled receptor 3 (GPR3), which was recently identified as a novel receptor for CBD. Our results showed that CBD inhibited inflammatory responses of astrocytes and microglia stimulated with lipopolysaccharide (LPS), a Toll-like receptor 4 (TLR4) ligand in vitro and in vivo. In addition, CBD reduced the phosphorylation of STAT3 and NF-κB signaling pathways in LPS-stimulated astrocytes. However, the inhibitory effect of CBD on pro-inflammatory cytokine production was independent of GPR3 expression in both types of glial cells. Thus, although CBD is effective in ameliorating the activation of astrocytes and microglia, its mechanism of action still requires further study. Our data support the concept that CBD may have therapeutic potential for neurological disorders that involve neuroinflammation.

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