Sodium hydrogen exchanger and phospholipase D are required for α1-adrenergic receptor stimulation of metalloproteinase-9 and cellular invasion in CCL39 fibroblasts

2008 ◽  
Vol 477 (1) ◽  
pp. 60-66 ◽  
Author(s):  
Jennifer Taves ◽  
Danielle Rastedt ◽  
Jenny Canine ◽  
Dave Mork ◽  
Mark A. Wallert ◽  
...  
Keyword(s):  
Phospholipase D ◽  
Adrenergic Receptor ◽  
Receptor Stimulation ◽  
Cellular Invasion ◽  
Sodium Hydrogen ◽  
Sodium Hydrogen Exchanger ◽  
Metalloproteinase 9 ◽  
Stimulation Of

Phospholipase C-β1 mediates α1-adrenergic receptor-stimulated activation of the sodium–hydrogen exchanger in Chinese hamster lung fibroblasts (CCL39)

2005 ◽  
Vol 83 (2) ◽  
pp. 123-132 ◽  
Author(s):  
J J Provost ◽  
S M Olmschenk ◽  
A L Metcalf ◽  
N Korpi ◽  
H Thronson ◽  
...  
Keyword(s):  
Phospholipase C ◽  
Cell Lines ◽  
Adrenergic Receptor ◽  
Chinese Hamster ◽  
Lung Fibroblasts ◽  
Specific Chemical ◽  
Sodium Hydrogen ◽  
Sodium Hydrogen Exchanger ◽  
Nhe1 Activity ◽  
Ccl39 Cells

The activation of the Na+–H+ exchanger 1 (NHE1) and extracellular-signal regulated kinase (ERK) phospho rylation in Chinese hamster lung fibroblasts (CCL39) was characterized in response to the specific α1-adrenergic agonist, phenylephrine (PE). Addition of 100 µmol PE/L increased the steady-state intracellular pH (pHi) by 0.16 ± 0.03 pH units, as well as increasing the phosphorylation of ERK. The response of NHE1 to PE in CCL39 cells was determined by the use of specific antagonists. Use of 2 specific chemical inhibitors of phosphoinositide-specific phospholipase C (PLC) reduced the ability of PE to activate either the exchanger or ERK. Studies were conducted in PLCβ-deficient cell lines derived from parental CCL39 cells. NHE1 activity in both mutant cell lines was increased in response to phorbal esters or lysophosphatidic acid, whereas the addition of PE only caused a minimal change in either pHi or ERK phosphorylation. These results, combined with reconstitution experiments with exogenously expressed PLCβ1, PLCβ2, or PLCβ3, revealed that stimulation of NHE1 activity by PE in CCL39 cells is a PLCβ1-coupled event. Furthermore, the data indicate that α1-adrenergic signaling of PLCβ is upstream of ERK activation. These data demonstrate that PLCβ1 is primarily involved in the activation of NHE1 in CCL39 fibroblasts.Key words: CCL39, sodium hydrogen exchanger, ERK, α1-adrenergic receptor, phospholipase Cβ.

scholarly journals Investigation of the specific α1‐adrenergic receptor pathway link to phosphorylation of sodium‐hydrogen exchanger by RhoA kinase

2007 ◽  
Vol 21 (6) ◽  
Author(s):  
David Luther Mork ◽  
Lisa Streitz ◽  
Robert Reames ◽  
Moses Wananu ◽  
Mark Wallert ◽  
...  
Keyword(s):  
Adrenergic Receptor ◽  
Sodium Hydrogen ◽  
Rhoa Kinase ◽  
Sodium Hydrogen Exchanger

scholarly journals Somatostatin regulates NHE8 protein expression via the ERK1/2 MAPK pathway in DSS-induced colitis mice

2016 ◽  
Vol 311 (5) ◽  
pp. G954-G963 ◽  
Author(s):  
Xiao Li ◽  
Lin Cai ◽  
Hua Xu ◽  
Chong Geng ◽  
Jing Lu ◽  
...  
Keyword(s):  
Mapk Pathway ◽  
Somatostatin Receptor ◽  
Mucosal Injury ◽  
Sodium Absorption ◽  
Colonic Tissue ◽  
Pathological Conditions ◽  
Sodium Hydrogen ◽  
Sodium Hydrogen Exchanger ◽  
First Time ◽  
Stimulation Of

Previous studies reported that administration of somatostatin (SST) to human patients mitigated their diarrheal symptoms. Octreotide (an analog of SST) treatment in animals resulted in upregulation of sodium/hydrogen exchanger 8 (NHE8). NHE8 is important for water/sodium absorption in the intestine, and loss of NHE8 function results in mucosal injury. Thus we hypothesized that NHE8 expression is inhibited during colitis and that SST treatment during pathological conditions can restore NHE8 expression. Our data showed for the first time that NHE8 is expressed in the human colonic tissue and that NHE8 expression is decreased in ulcerative colitis (UC) patients. We also found that octreotide could stimulate colonic NHE8 expression in colitic mice. Furthermore, the somatostatin receptor 2 (SSTR2) agonist seglitide and the somatostatin receptor 5 (SSTR5) agonist L-817,818 could restore NHE8 expression via its role in suppressing ERK1/2 phosphorylation. Our study uncovered a novel mechanism of SST stimulation of NHE8 expression in colitis.

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