Use of Small-Molecule Crystal Structures To Address Solubility in a Novel Series of G Protein Coupled Receptor 119 Agonists: Optimization of a Lead and in Vivo Evaluation

2012 ◽  
Vol 55 (11) ◽  
pp. 5361-5379 ◽  
Author(s):  
James S. Scott ◽  
Alan M. Birch ◽  
Katy J. Brocklehurst ◽  
Anders Broo ◽  
Hayley S. Brown ◽  
...  
Keyword(s):  
Crystal Structures ◽  
G Protein ◽  
Small Molecule ◽  
G Protein Coupled Receptor ◽  
In Vivo Evaluation ◽  
G Protein Coupled

scholarly journals Systematic generation of in vivo G protein-coupled receptor mutants in the rat

2010 ◽  
Vol 11 (5) ◽  
pp. 326-336 ◽  
Author(s):  
R van Boxtel ◽  
B Vroling ◽  
P Toonen ◽  
I J Nijman ◽  
H van Roekel ◽  
...  
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

scholarly journals Roles of GP33, a guinea pig cytomegalovirus-encoded G protein-coupled receptor homolog, in cellular signaling, viral growth and inflammation in vitro and in vivo

2018 ◽  
Vol 14 (12) ◽  
pp. e1007487 ◽  
Author(s):  
Miei Takeda ◽  
Shinji Watanabe ◽  
Harutaka Katano ◽  
Kazuma Noguchi ◽  
Yuko Sato ◽  
...  
Keyword(s):  
Guinea Pig ◽  
G Protein ◽  
Cellular Signaling ◽  
G Protein Coupled Receptor ◽  
Viral Growth ◽  
Guinea Pig Cytomegalovirus ◽  
G Protein Coupled

scholarly journals Hybrid Transgenic Mice Reveal In Vivo Specificity of G Protein–Coupled Receptor Kinases in the Heart

2000 ◽  
Vol 86 (1) ◽  
pp. 43-50 ◽  
Author(s):  
Andrea D. Eckhart ◽  
Sandra J. Duncan ◽  
Raymond B. Penn ◽  
Jeffrey L. Benovic ◽  
Robert J. Lefkowitz ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
G Protein ◽  
G Protein Coupled Receptor ◽  
Receptor Kinases ◽  
G Protein Coupled

scholarly journals GAIN domain–mediated cleavage is required for activation of G protein–coupled receptor 56 (GPR56) by its natural ligands and a small-molecule agonist

2019 ◽  
Vol 294 (50) ◽  
pp. 19246-19254 ◽  
Author(s):  
Beika Zhu ◽  
Rong Luo ◽  
Peng Jin ◽  
Tao Li ◽  
Hayeon C. Oak ◽  
...  
Keyword(s):  
G Protein ◽  
Small Molecule ◽  
G Protein Coupled Receptor ◽  
Natural Ligands ◽  
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.

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