scholarly journals Regulated Expression of pH Sensing G Protein-Coupled Receptor-68 Identified through Chemical Biology Defines a New Drug Target for Ischemic Heart Disease

2012 ◽  
Vol 7 (6) ◽  
pp. 1077-1083 ◽  
Author(s):  
Jamie L. Russell ◽  
Sean C. Goetsch ◽  
Hector R. Aguilar ◽  
Helen Coe ◽  
Xiang Luo ◽  
...  
Keyword(s):  
Heart Disease ◽  
Ischemic Heart Disease ◽  
G Protein ◽  
Drug Target ◽  
Chemical Biology ◽  
Ischemic Heart ◽  
Ph Sensing ◽  
G Protein Coupled Receptor ◽  
Regulated Expression ◽  
G Protein Coupled

scholarly journals Adenosine G Protein‐Coupled Receptor Biased Agonism to Treat Ischemic Heart Disease

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Lauren Therese May ◽  
Jo‐Anne Baltos ◽  
Chung H. Chuo ◽  
Elizabeth A. Vecchio ◽  
Bing H. Wang ◽  
...  
Keyword(s):  
Heart Disease ◽  
Ischemic Heart Disease ◽  
G Protein ◽  
Ischemic Heart ◽  
G Protein Coupled Receptor ◽  
Biased Agonism ◽  
G Protein Coupled

scholarly journals Vascular Abnormalities in Mice Deficient for the G Protein-Coupled Receptor GPR4 That Functions as a pH Sensor

2006 ◽  
Vol 27 (4) ◽  
pp. 1334-1347 ◽  
Author(s):  
Li V. Yang ◽  
Caius G. Radu ◽  
Meenakshi Roy ◽  
Sunyoung Lee ◽  
Jami McLaughlin ◽  
...  
Keyword(s):  
G Protein ◽  
Mesangial Cells ◽  
Ex Vivo ◽  
Extracellular Ph ◽  
Ph Sensing ◽  
G Protein Coupled Receptor ◽  
Vascular Abnormalities ◽  
G Protein Coupled

ABSTRACT GPR4 is a G protein-coupled receptor expressed in the vasculature, lung, kidney, and other tissues. In vitro ectopic overexpression studies implicated GPR4 in sensing extracellular pH changes leading to cyclic AMP (cAMP) production. To investigate its biological roles in vivo, we generated GPR4-deficient mice by homologous recombination. Whereas GPR4-null adult mice appeared phenotypically normal, neonates showed a higher frequency of perinatal mortality. The average litter size from GPR4−/− intercrosses was ∼30% smaller than that from GPR4+/+ intercrosses on N3 and N5 C57BL/6 genetic backgrounds. A fraction of knockout embryos and neonates had spontaneous hemorrhages, dilated and tortuous subcutaneous blood vessels, and defective vascular smooth muscle cell coverage. Mesangial cells in kidney glomeruli were also significantly reduced in GPR4-null neonates. Some neonates exhibited respiratory distress with airway lining cell metaplasia. To examine whether GPR4 is functionally involved in vascular pH sensing, an ex vivo aortic ring assay was used under defined pH conditions. Compared to wild-type aortas, microvessel outgrowth from GPR4-null aortas was less inhibited by acidic extracellular pH. Treatment with an analog of cAMP, a downstream effector of GPR4, abolished microvessel outgrowth bypassing the GPR4-knockout phenotype. These results suggest that GPR4 deficiency leads to partially penetrant vascular abnormalities during development and that this receptor functions in blood vessel pH sensing.

scholarly journals Mitochondria as a Drug Target in Ischemic Heart Disease and Cardiomyopathy

2012 ◽  
Vol 111 (9) ◽  
pp. 1222-1236 ◽  
Author(s):  
Andrew M. Walters ◽  
George A. Porter ◽  
Paul S. Brookes
Keyword(s):  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Drug Target ◽  
Ischemic Heart

scholarly journals Hypoxia Positively Regulates the Expression of pH-Sensing G-Protein–Coupled Receptor OGR1 (GPR68)

2016 ◽  
Vol 2 (6) ◽  
pp. 796-810 ◽  
Author(s):  
Cheryl de Vallière ◽  
Jesus Cosin-Roger ◽  
Simona Simmen ◽  
Kirstin Atrott ◽  
Hassan Melhem ◽  
...  
Keyword(s):  
G Protein ◽  
Ph Sensing ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

The Role of the RS8005161 Polymorphism on pH-Sensing G Protein-Coupled Receptor GPR65 (TDAG8) Signalling in Intestinal Inflammation

2017 ◽  
Vol 152 (5) ◽  
pp. S758-S759
Author(s):  
Irina Tcymbarevich ◽  
Nicole M. Obialo ◽  
Jesus Cosin-Roger ◽  
Klaus Seuwen ◽  
Gerhard Rogler ◽  
...  
Keyword(s):  
G Protein ◽  
Intestinal Inflammation ◽  
Ph Sensing ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

scholarly journals P072 The role of the rs8005161 polymorphism on pH-sensing G protein-coupled receptor GPR65 (TDAG8) signalling in intestinal inflammation

2017 ◽  
Vol 11 (suppl_1) ◽  
pp. S113-S113
Author(s):  
I. Tcymbarevich ◽  
N. Obialo ◽  
J. Cosin-Roger ◽  
K. Seuwen ◽  
G. Rogler ◽  
...  
Keyword(s):  
G Protein ◽  
Intestinal Inflammation ◽  
Ph Sensing ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

scholarly journals Evidence for a Bacterial Lipopolysaccharide-Recognizing G-Protein-Coupled Receptor in the Bacterial Engulfment by Entamoeba histolytica

2013 ◽  
Vol 12 (11) ◽  
pp. 1433-1438 ◽  
Author(s):  
Matthew T. Brewer ◽  
Prince N. Agbedanu ◽  
Mostafa Zamanian ◽  
Tim A. Day ◽  
Steve A. Carlson
Keyword(s):  
G Protein ◽  
Entamoeba Histolytica ◽  
Drug Target ◽  
Bacterial Flora ◽  
Bacterial Lipopolysaccharide ◽  
Dependent Manner ◽  
G Protein Coupled Receptor ◽  
Concentration Dependent Manner ◽  
Content Type ◽  
G Protein Coupled

ABSTRACT Entamoeba histolytica is the causative agent of amoebic dysentery, a worldwide protozoal disease that results in approximately 100,000 deaths annually. The virulence of E. histolytica may be due to interactions with the host bacterial flora, whereby trophozoites engulf colonic bacteria as a nutrient source. The engulfment process depends on trophozoite recognition of bacterial epitopes that activate phagocytosis pathways. E. histolytica GPCR-1 (EhGPCR-1) was previously recognized as a putative G-protein-coupled receptor (GPCR) used by Entamoeba histolytica during phagocytosis. In the present study, we attempted to characterize EhGPCR-1 by using heterologous GPCR expression in Saccharomyces cerevisiae . We discovered that bacterial lipopolysaccharide (LPS) is an activator of EhGPCR-1 and that LPS stimulates EhGPCR-1 in a concentration-dependent manner. Additionally, we demonstrated that Entamoeba histolytica prefers to engulf bacteria with intact LPS and that this engulfment process is sensitive to suramin, which prevents the interactions of GPCRs and G-proteins. Thus, EhGPCR-1 is an LPS-recognizing GPCR that is a potential drug target for treatment of amoebiasis, especially considering the well-established drug targeting to GPCRs.

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