Dopamine D1-like Receptor-Mediated Inhibition of Cl-/HCO3- Exchanger Activity in Rat Intestinal Epithelial IEC-6 Cells is Regulated by G Protein-Coupled Receptor Kinase 6 (GRK 6)

2006 ◽  
Vol 18 (6) ◽  
pp. 347-360 ◽  
Author(s):  
Sonia Fraga ◽  
Yingjin Luo ◽  
Pedro Jose ◽  
Kambiz Zandi-Nejad ◽  
David Mount ◽  
...  
Keyword(s):  
G Protein ◽  
Intestinal Epithelial ◽  
Receptor Kinase ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

Involvement of G protein-coupled receptor kinase 4 and 6 in rapid desensitization of dopamine D1 receptor in rat IEC-6 intestinal epithelial cells

2004 ◽  
Vol 287 (4) ◽  
pp. R772-R779 ◽  
Author(s):  
Sónia Fraga ◽  
Pedro A. Jose ◽  
Patrício Soares-da-Silva
Keyword(s):  
G Protein ◽  
D1 Receptor ◽  
Skf 38393 ◽  
Epithelial Cell Line ◽  
Intestinal Epithelial ◽  
Receptor Kinase ◽  
G Protein Coupled Receptor ◽  
Dependent Inhibition ◽  
G Protein Coupled ◽  
Stimulation Of

Dopamine-induced inhibition of Na+-K+-ATPase has been suggested to play a role in the regulation of Na+ absorption at the intestinal level, and these effects were mediated by dopamine D1-like receptors. The aim of this work was to evaluate the effect of the activation of the D1-like receptors on the activity of the Na+/H+ exchanger (NHE) in the rat intestinal epithelial cell line IEC-6. The presence of D1 receptors was confirmed by immunoblotting. The dopamine D1-like receptor agonist SKF-38393 produced a concentration-dependent inhibition of NHE activity and stimulation of adenylyl cyclase (AC), this being antagonized by the D1 selective antagonist SKF-83566. Effects of SKF-38393 on NHE and AC activities were maximal at 5 min of exposure to the agonist and rapidly diminished with no effect at 25 min. Exposure of cells for 25 min to dibutyryl-cAMP (0.5 mM) or to the AC activator forskolin (3 μM) effectively inhibited NHE activity. Pretreatment of cells with heparin (1 μM), a nonselective G protein-coupled receptor kinase (GRK) inhibitor, prevented the loss of effects on NHE activity after 25 min exposure to SKF-38393. The presence of GRK4, GRK6A, and GRK6B was confirmed by immunoblotting. Overnight treatment with the anti-GRK4–6 antibody complexed with Lipofectin was also effective in preventing loss of the effects of SKF-38393 on NHE and AC activities. It is concluded that dopamine D1 receptors in IEC-6 rapidly desensitize to D1-like agonist stimulation and GRK4 and 6 appear to be involved in agonist-mediated responsiveness and desensitization.

scholarly journals Structural Determinants Influencing the Potency and Selectivity of Indazole-Paroxetine Hybrid G Protein–Coupled Receptor Kinase 2 Inhibitors

2017 ◽  
Vol 92 (6) ◽  
pp. 707-717 ◽  
Author(s):  
Renee Bouley ◽  
Helen V. Waldschmidt ◽  
M. Claire Cato ◽  
Alessandro Cannavo ◽  
Jianliang Song ◽  
...  
Keyword(s):  
G Protein ◽  
Receptor Kinase ◽  
G Protein Coupled Receptor ◽  
Structural Determinants ◽  
G Protein Coupled

scholarly journals Generation of Highly Selective, Potent, and Covalent G Protein-Coupled Receptor Kinase 5 Inhibitors

2021 ◽  
Author(s):  
Rachel A. Rowlands ◽  
Qiuyan Chen ◽  
Renee A. Bouley ◽  
Larisa V. Avramova ◽  
John J. G. Tesmer ◽  
...  
Keyword(s):  
G Protein ◽  
Receptor Kinase ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled
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