scholarly journals Evidence of an essential role of NHERF1 and NHEF2 in G‐protein coupled receptor regulation of CFTR‐mediated intestinal anion secretion in vivo

2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Anurag Kumar Singh ◽  
Brigitte Riederer ◽  
Hugo R. Jonge ◽  
Mark Donowitz ◽  
Edward J. Weinman ◽  
...  
Keyword(s):  
G Protein ◽  
Essential Role ◽  
Receptor Regulation ◽  
G Protein Coupled Receptor ◽  
Anion Secretion ◽  
G Protein Coupled

scholarly journals Role of Endothelial G Protein-Coupled Receptor Kinase 2 in Angioedema

Hypertension ◽  
2020 ◽  
Vol 76 (5) ◽  
pp. 1625-1636 ◽  
Author(s):  
Jessica Gambardella ◽  
Daniela Sorriento ◽  
Maria Bova ◽  
Mariarosaria Rusciano ◽  
Stefania Loffredo ◽  
...  
Keyword(s):  
Vascular Permeability ◽  
G Protein ◽  
Molecular Mechanisms ◽  
No Production ◽  
Receptor Kinase ◽  
Severe Phenotype ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

Excessive BK (bradykinin) stimulation is responsible for the exaggerated permeabilization of the endothelium in angioedema. However, the molecular mechanisms underlying these responses have not been investigated. BK receptors are Gq-protein-coupled receptors phosphorylated by GRK2 (G protein-coupled receptor kinase 2) with a hitherto unknown biological and pathophysiological significance. In the present study, we sought to identify the functional role of GRK2 in angioedema through the regulation of BK signaling. We found that the accumulation of cytosolic Ca 2+ in endothelial cells induced by BK was sensitive to GRK2 activity, as it was significantly augmented by inhibiting the kinase. Accordingly, permeabilization and NO production induced by BK were enhanced, as well. In vivo, mice with reduced GRK2 levels in the endothelium (Tie2-CRE/GRK2 fl+/fl − ) exhibited an increased response to BK in terms of vascular permeability and extravasation. Finally, patients with reduced GRK2 levels displayed a severe phenotype of angioedema. Taken together, these findings establish GRK2 as a novel pivotal regulator of BK signaling with an essential role in the pathophysiology of vascular permeability and angioedema.

scholarly journals Role of G protein-coupled receptor 1 in choriocarcinoma progression

2019 ◽  
Vol 317 (3) ◽  
pp. C556-C565 ◽  
Author(s):  
Binbin Huang ◽  
Wen Zhu ◽  
Junlei Chang ◽  
Xiaoyong Dai ◽  
Guiyuan Yu ◽  
...  
Keyword(s):  
G Protein ◽  
Drug Distribution ◽  
Chemotherapeutic Agents ◽  
G Protein Coupled Receptor ◽  
Amino Acid Peptide ◽  
Erk Phosphorylation ◽  
G Protein Coupled

Choriocarcinoma is characterized by malignant proliferation and transformation of trophoblasts and is currently treated with systemic chemotherapeutic agents. The lack of specific targets for chemotherapeutic agents results in indiscriminate drug distribution. In our study, we aimed to delineate the mechanism by which G protein-coupled receptor 1 (GPR1) regulates the development of choriocarcinoma and thus investigated GPR1 as a prospective chemotherapeutic target. In this study, GPR1 expression levels were examined in several trophoblast cell lines. We found significantly higher GPR1 expression in choriocarcinoma cells (JEG3 and BeWo) than in normal trophoblast cells (HTR-8/SVneo). Additionally, we studied the role of GPR1 in choriocarcinoma in vitro and in vivo. GPR1 knockdown suppressed proliferation, invasion, and Akt and ERK phosphorylation in vitro and slowed tumor growth in vivo. Interestingly, GPR1 overexpression promoted increased proliferation, invasion, and Akt and ERK phosphorylation in vitro. Furthermore, we identified a specific GPR1-binding seven-amino acid peptide, LRH7-G3, that might also suppress choriocarcinoma in vitro and in vivo through phage display. Our study is the first to report that GPR1 may play a role in regulating choriocarcinoma progression through the Akt and ERK pathways. GPR1 could be a promising potential pharmaceutical target for choriocarcinoma.

scholarly journals Evaluation of the role of the retinal G protein-coupled receptor (RGR) in the vertebrate retina in vivo

2003 ◽  
Vol 85 (4) ◽  
pp. 944-956 ◽  
Author(s):  
Tadao Maeda ◽  
J. Preston Van Hooser ◽  
Carola A. G. G. Driessen ◽  
Sławomir Filipek ◽  
Jacques J. M. Janssen ◽  
...  
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptor ◽  
Vertebrate Retina ◽  
G Protein Coupled
Sign in / Sign up

Export Citation Format

Share Document