scholarly journals Identification of Physiologically Active Substances as Novel Ligands for MRGPRD

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Makiko Uno ◽  
Satoko Nishimura ◽  
Keisuke Fukuchi ◽  
Yasuyuki Kaneta ◽  
Yoko Oda ◽  
...  
Keyword(s):  
G Protein ◽  
Anticancer Agent ◽  
The Novel ◽  
G Protein Coupled Receptor ◽  
Chemical Library ◽  
Beta Alanine ◽  
Physiologically Active Substances ◽  
Small Molecule Compound ◽  
G Protein Coupled ◽  
Active Substances

Mas-related G-protein coupled receptor member D (MRGPRD) is a G protein-coupled receptor (GPCR) which belongs to the Mas-related GPCRs expressed in the dorsal root ganglia (DRG). In this study, we investigated two novel ligands in addition to beta-alanine: (1) beta-aminoisobutyric acid, a physiologically active substance, with which possible relation to tumors has been seen together with beta-alanine; (2) diethylstilbestrol, a synthetic estrogen hormone. In addition to the novel ligands, we found that transfection of MRGPRD leads fibroblast cells to form spheroids, which would be related to oncogenicity. To understand the MRGPRD novel character, oncogenicity, a large chemical library was screened in order to obtain MRGPRD antagonists to utilize in exploring the character. The antagonist in turn inhibited the spheroid proliferation that is dependent on MRGPRD signaling as well as MRGPRD signals activated by beta-alanine. The antagonist, a small-molecule compound we found in this study, is a potential anticancer agent.

scholarly journals Interactions of the G protein-coupled receptor-associated sorting proteins (GASP) 1 and 2 with the novel cannabinoid receptor GPR55

2008 ◽  
Vol 8 (Suppl 1) ◽  
pp. A16
Author(s):  
Julia Kargl ◽  
Nariman Balenga ◽  
Lene Martini ◽  
Jennifer Whistler ◽  
Maria Waldhoer
Keyword(s):  
G Protein ◽  
Cannabinoid Receptor ◽  
The Novel ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

The novel G-protein coupled receptor SALPR shares sequence similarity with somatostatin and angiotensin receptors

Gene ◽  
2000 ◽  
Vol 248 (1-2) ◽  
pp. 183-189 ◽  
Author(s):  
Mitsuyuki Matsumoto ◽  
Masazumi Kamohara ◽  
Toru Sugimoto ◽  
Kazuyuki Hidaka ◽  
Jun Takasaki ◽  
...  
Keyword(s):  
G Protein ◽  
Sequence Similarity ◽  
Angiotensin Receptors ◽  
The Novel ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

scholarly journals A sexually dimorphic distribution pattern of the novel estrogen receptor G-protein-coupled receptor 30 in some brain areas of the hamster

2007 ◽  
Vol 196 (1) ◽  
pp. 131-138 ◽  
Author(s):  
Marcello Canonaco ◽  
Giuseppina Giusi ◽  
Antonio Madeo ◽  
Rosa Maria Facciolo ◽  
Rosamaria Lappano ◽  
...  
Keyword(s):  
G Protein ◽  
Expression Pattern ◽  
Gene Expression Pattern ◽  
Membrane Receptor ◽  
Sexually Dimorphic ◽  
The Novel ◽  
G Protein Coupled Receptor ◽  
Brain Areas ◽  
Adult Hamster ◽  
G Protein Coupled

The isolation of the G-protein-coupled receptor 30 (GPR30), an orphan membrane receptor unrelated to nuclear estrogen receptors (ERs), has become a key factor towards the unraveling of rapid estrogen action. This membrane receptor together with cellular signaling intermediaries, i.e., extracellular signal-dependent kinases 1 and 2, may promote neuronal proliferation and differentiation activities. In the present study, an evident gene expression pattern of GPR30 characterized postnatal 7 (young) and 60 (adult) days of age hamsters as shown by its heterogeneous mRNA distribution in hypothalamic, amygdalar and cerebellar areas of both sexes. In particular, most of the brain areas considered in the adult hamster plus only the amygdala and cerebellum of young animals behaved in a sexually dimorphic fashion. This similar pattern was also detected for the ERα and β, as shown by the latter receptor prevailing in young and adult females, while the former predominated in young females. Even for the two kinases, a sexually dimorphic distribution was featured above all for young hamsters. Overall, the findings of the present study established a distinct expression pattern of the novel ER (GPR30) that may operate differently in some brain areas of the hamster and this may provide interesting insights regarding its probable neuroprotective role during the execution of some hibernating states, which are typical of our rodent model.

scholarly journals Inhibition of Ebola and Marburg Virus Entry by G Protein-Coupled Receptor Antagonists

2015 ◽  
Vol 89 (19) ◽  
pp. 9932-9938 ◽  
Author(s):  
Han Cheng ◽  
Calli M. Lear-Rooney ◽  
Lisa Johansen ◽  
Elizabeth Varhegyi ◽  
Zheng W. Chen ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
G Protein ◽  
High Mortality ◽  
Ebola Virus ◽  
Critical Role ◽  
Marburg Virus ◽  
Severe Illness ◽  
G Protein Coupled Receptor ◽  
Chemical Library ◽  
G Protein Coupled

ABSTRACTFiloviruses, consisting of Ebola virus (EBOV) and Marburg virus (MARV), are among the most lethal infectious threats to mankind. Infections by these viruses can cause severe hemorrhagic fevers in humans and nonhuman primates with high mortality rates. Since there is currently no vaccine or antiviral therapy approved for humans, there is an urgent need to develop prophylactic and therapeutic options for use during filoviral outbreaks and bioterrorist attacks. One of the ideal targets against filoviral infection and diseases is at the entry step, which is mediated by the filoviral glycoprotein (GP). In this report, we screened a chemical library of small molecules and identified numerous inhibitors, which are known G protein-coupled receptor (GPCR) antagonists targeting different GPCRs, including histamine receptors, 5-HT (serotonin) receptors, muscarinic acetylcholine receptor, and adrenergic receptor. These inhibitors can effectively block replication of both infectious EBOV and MARV, indicating a broad antiviral activity of the GPCR antagonists. The time-of-addition experiment and microscopic studies suggest that GPCR antagonists block filoviral entry at a step following the initial attachment but prior to viral/cell membrane fusion. These results strongly suggest that GPCRs play a critical role in filoviral entry and GPCR antagonists can be developed as an effective anti-EBOV/MARV therapy.IMPORTANCEInfection of Ebola virus and Marburg virus can cause severe illness in humans with a high mortality rate, and currently there is no FDA-approved vaccine or therapeutic treatment available. The 2013-2015 epidemic in West Africa underscores a lack of our understanding in the infection and pathogenesis of these viruses and the urgency of drug discovery and development. In this study, we have identified numerous inhibitors that are known G protein-coupled receptor (GPCR) antagonists targeting different GPCRs. These inhibitors can effectively block replication of both infectious EBOV and MARV, indicating a broad antiviral activity of the GPCR antagonists. Our results strongly suggest that GPCRs play a critical role in filoviral entry and GPCR antagonists can be developed as an effective anti-EBOV/MARV therapy.

scholarly journals The novel estrogen receptor G-protein-coupled receptor 30 is expressed in human bone

2008 ◽  
Vol 197 (2) ◽  
pp. R1-R6 ◽  
Author(s):  
Terhi J Heino ◽  
Andrei S Chagin ◽  
Lars Sävendahl
Keyword(s):  
G Protein ◽  
Bone Cells ◽  
Mineral Metabolism ◽  
Pubertal Development ◽  
Linear Regression Analysis ◽  
Estrogen Signaling ◽  
The Novel ◽  
G Protein Coupled Receptor ◽  
Bone Biopsies ◽  
G Protein Coupled

Estrogens have significant impact on bone mineral metabolism. Besides the classical estrogen receptors (ERα and ERβ), a trans-membrane G-protein-coupled receptor (GPR30) has been demonstrated to mediate estrogenic effects. We aimed to study whether GPR30 is expressed in bone cells and if so, whether the level of expression is developmentally regulated. Metaphyseal bone biopsies were collected from the tibia in 14 boys and 6 girls, all at different stages of puberty. GPR30 protein expression was studied by immunohistochemistry in paraffin-embedded sections. GPR30-positive osteocytes and osteoblasts were quantified and linear regression analysis was applied. Cytoplasmic GPR30 expression was detected in osteoblasts, osteocytes, and osteoclasts. Osteocytes were more frequently positive for GPR30 than osteoblasts (58±4% vs 46±3% positive cells respectively, P<0.05). Detailed analysis demonstrated that GPR30 positivity declined during pubertal development in osteocytes (R=−0.56, P<0.01) but not in osteoblasts (R=−0.31, P>0.05). No sex difference was observed in the numbers of GPR30-positive osteoblasts or osteocytes. Furthermore, GPR30 expression did not correlate with chronological or bone age. In conclusion, the novel ER GPR30 is expressed in osteoblasts, osteocytes, and osteoclasts suggesting that non-genomic estrogen signaling via GPR30 may exist in bone. However, the functional role of GPR30 in bone tissue remains to be elucidated.

scholarly journals The Novel Functions of the PLC/PKC/PKD Signaling Axis in G Protein-Coupled Receptor-Mediated Chemotaxis of Neutrophils

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Xuehua Xu ◽  
Tian Jin
Keyword(s):  
Cell Migration ◽  
Signaling Pathway ◽  
G Protein ◽  
Essential Role ◽  
The Novel ◽  
G Protein Coupled Receptor ◽  
Signaling Axis ◽  
Extracellular Stimuli ◽  
Directional Cell Migration ◽  
G Protein Coupled

Chemotaxis, a directional cell migration guided by extracellular chemoattractant gradients, plays an essential role in the recruitment of neutrophils to sites of inflammation. Chemotaxis is mediated by the G protein-coupled receptor (GPCR) signaling pathway. Extracellular stimuli trigger activation of the PLC/PKC/PKD signaling axis, which controls several signaling pathways. Here, we concentrate on the novel functions of PLC/PKC/PKD signaling in GPCR-mediated chemotaxis of neutrophils.

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