Bradykinin- and substance P-induced edema formation in the hamster cheek pouch is tyrosine kinase dependent

2007 ◽  
Vol 103 (1) ◽  
pp. 184-189 ◽  
Author(s):  
Israel Rubinstein
Keyword(s):  
Substance P ◽  
Tyrosine Kinase ◽  
Intracellular Signaling ◽  
Protein Tyrosine Kinase ◽  
Cell Function ◽  
Cheek Pouch ◽  
Induced Responses ◽  
Hamster Cheek Pouch ◽  
Endothelial Cell Function ◽  
Protein Tyrosine

The purpose of this study was to determine whether protein tyrosine kinase, a ubiquitous family of intracellular signaling enzymes that regulates endothelial cell function, modulates bradykinin- and substance P-induced increase in macromolecular efflux from the intact hamster cheek pouch microcirculation. Using intravital microscopy, I found that suffusion of bradykinin or substance P (each, 0.5 and 1.0 μM) onto the cheek pouch elicited significant, concentration-dependent leaky site formation and increase in clearance of fluorescein isothiocyanate-dextran (FITC-dextran; molecular mass, 70 kDa; P < 0.05). These responses were significantly attenuated by suffusion of genistein (1.0 μM) or tyrphostin 25 (10 μM), two structurally unrelated, nonspecific protein tyrosine kinase inhibitors ( P < 0.05). Conceivably, the kinase(s) involved in this process could be agonist specific because genistein was more effective than tyrphostin 25 in attenuating bradykinin-induced responses while the opposite was observed with substance P. Both inhibitors had no significant effects on adenosine (0.5 M)-induced responses ( P > 0.5). Collectively, these data suggest that the protein tyrosine kinase metabolic pathway modulates, in part, the edemagenic effects of bradykinin and substance P in the intact hamster cheek pouch microcirculation in a specific fashion.

Platelet-activating factor stimulates protein tyrosine kinase in hamster cheek pouch microcirculation

1995 ◽  
Vol 268 (1) ◽  
pp. H399-H403 ◽  
Author(s):  
D. Kim ◽  
W. N. Duran
Keyword(s):  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Platelet Activating Factor ◽  
Fluorescein Isothiocyanate ◽  
Cheek Pouch ◽  
Computer Assisted ◽  
Hamster Cheek Pouch ◽  
Protein Tyrosine ◽  
Macromolecular Transport ◽  
Arteriolar Tone

We studied the interactions between platelet-activating factor (PAF) and protein tyrosine kinase (PTK) in the modulation of microvascular responses in the hamster cheek pouch using intravital microscopy and computer-assisted image analysis. Changes in arteriolar diameter and in integrated optical intensity (IOI; an index of vascular permeability) were measured. Fluorescein isothiocyanate-labeled dextran 150 (FITC-Dx 150) served as a tracer for macromolecular transport. Genistein and tyrphostin 25, two PTK inhibitors, were applied topically in separate experiments. Pretreatment with 10(-4), 10(-6), and 10(-8) M genistein and with tyrphostin 25 at 10(-5) and 10(-7) M attenuated the maximal increment in mean IOI (+/- SE) induced by PAF at 10(-7) M (19.9 +/- 5.3, 21.5 +/- 4.5, 58.5 +/- 11.4, 28.7 +/- 7.6, and 35.0 +/- 10.9 vs. 70.7 +/- 8.9 units, respectively). Pretreatment with PTK inhibitors resulted in vasodilation but did not inhibit PAF-induced vasoconstriction. Our results suggest that PTK represents a biochemical pathway involved in the PAF modulation of microvascular permeability but not PAF modulation of arteriolar tone.

The GPI-anchored adhesion molecule F3 induces tyrosine phosphorylation: involvement of the FNIII repeats

1996 ◽  
Vol 109 (3) ◽  
pp. 699-704 ◽  
Author(s):  
M. Cervello ◽  
V. Matranga ◽  
P. Durbec ◽  
G. Rougon ◽  
S. Gomez
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Phosphorylation ◽  
Cho Cells ◽  
Intracellular Signaling ◽  
Protein Tyrosine Kinase ◽  
Cross Linking ◽  
Protein Tyrosine ◽  
Intracellular Signaling Pathway ◽  
Type Iii ◽  
Cell Cell

The glycosyl-phosphatidylinositol (GPI)-anchored F3 molecule, a member of the Ig superfamily made up of Ig and FNIII-like domains, is involved in cell-cell adhesion, neuronal pathfinding and fasciculation. Little is known about the mechanism(s) that governs the F3-mediated cell-cell recognition. In particular, it is not known whether F3 transduces signals across the membrane. Here we show that in F3-transfected CHO cells (1A cells) an increase in tyrosine phosphorylation occurs during F3-mediated aggregation. Moreover, under aggregation conditions F3 immunoprecipitated from 32P-metabolically labeled 1A cells associated with three major phosphorylated proteins. Interestingly, genistein inhibited the F3-mediated aggregation. Increased tyrosine phosphorylation was also observed using antibody-mediated F3-cross-linking. Furthermore, F3 expressed both in 1A cells and in post-natal mouse cerebellum forms non-covalent soluble complexes with protein tyrosine kinase(s). In cerebellum the F3-associated kinase was identified as fyn. By contrast, a truncated F3 protein, expressed in CHO cells, from which all the FN type III repeats have been deleted, does not associate with a kinase. Cross-linking of the F3-truncated form does not induce modulation of tyrosine phosphorylation. Taken together these data demonstrate that F3 is a molecule that transduces signals through both association with protein tyrosine kinase and modulation of protein tyrosine phosphorylation. The presence of FN type III domains is essential for the activation of the intracellular signaling pathway.

Neutral endopeptidase modulates substance P-induced vasodilation in vivo

1995 ◽  
Vol 78 (2) ◽  
pp. 562-568 ◽  
Author(s):  
X. P. Gao ◽  
I. Rubinstein
Keyword(s):  
Substance P ◽  
Oral Mucosa ◽  
Intravital Microscopy ◽  
Neutral Endopeptidase ◽  
Cheek Pouch ◽  
Induced Responses ◽  
Hamster Cheek Pouch ◽  
Arteriolar Diameter ◽  
Significant Concentration

The purpose of this study was to investigate whether neutral endopeptidase (NEP; EC 3.4.24.11) modulates substance P-induced vasodilation in the oral mucosa in vivo. Using intravital microscopy, we measured the diameter of second-order arterioles (44–70 microns) in the hamster cheek pouch during suffusion of capsaicin and substance P. We found that capsaicin (0.1 and 10.0 nM) induced significant concentration-dependent vasodilations (13 +/- 4 and 39 +/- 7% increase from baseline, respectively; P < 0.05) that were significantly potentiated by phosphoramidon (10.0 nM), a selective NEP inhibitor (35 +/- 15 and 61 +/- 12% increase from baseline, respectively; P < 0.05). Substance P (0.1 and 10.0 nM) also induced significant concentration-dependent vasodilations (7 +/- 3 and 25 +/- 8% increase from baseline, respectively; P < 0.05) that were mediated by the COOH-terminal of the molecule. Substance P-induced responses were significantly potentiated by phosphoramidon (34 +/- 9 and 53 +/- 10% increase from baseline, respectively; P < 0.05) and thiorphan (10.0 microM), a selective NEP inhibitor (44 +/- 11 and 53 +/- 10% increase from baseline, respectively; P < 0.05). Substance P-(1–9) had no significant effects on arteriolar diameter. Suffusion of captopril, leupeptin, Bestatin, and DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid together had no significant effects on substance P-induced vasodilation. Phosphoramidon did not potentiate nitroglycerin-induced vasodilation. These data indicate that NEP modulates substance P-induced vasodilation in the hamster cheek pouch in vivo. We suggest that any decrease in tissue NEP activity may amplify neurogenic vasodilation in the oral mucosa.

The protein tyrosine kinase Tec regulates mast cell function

2009 ◽  
Vol 39 (11) ◽  
pp. 3228-3238 ◽  
Author(s):  
Uwe Schmidt ◽  
Anastasia Abramova ◽  
Nicole Boucheron ◽  
Eva Eckelhart ◽  
Alexandra Schebesta ◽  
...  
Keyword(s):  
Mast Cell ◽  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Cell Function ◽  
Protein Tyrosine

scholarly journals Sodium and potassium regulate endothelial phospholipase C-γ and Bmx

2014 ◽  
Vol 307 (1) ◽  
pp. F58-F63 ◽  
Author(s):  
Wei-Zhong Ying ◽  
Kristal J. Aaron ◽  
Paul W. Sanders
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Tyrosine Kinase ◽  
Phospholipase C ◽  
Intracellular Signaling ◽  
Cell Function ◽  
Pleckstrin Homology Domain ◽  
Endothelial Cell Function ◽  
Salt Diet

The amount of Na+ and K+ in the diet promotes significant changes in endothelial cell function. In the present study, a series of in vitro and in vivo experiments determined the role of Na+ and K+ in the regulation of two pleckstrin homology domain-containing intracellular signaling molecules, phospholipase C (PLC)-γ1 and epithelial and endothelial tyrosine kinase/bone marrow tyrosine kinase on chromosome X (Bmx), and agonist-generated Ca2+ signaling in the endothelium. Extracellular K+ concentration regulated the levels of activated PLC-γ1, Bmx, and carbachol-stimulated intracellular Ca2+ mobilization in human endothelial cells. Additional experiments confirmed that high-conductance Ca2+-activated K+ channels and phosphatidylinositol 3-kinase mediated these effects. The content of Na+ and K+ in the diet also regulated Bmx levels in endothelial cells and activated PLC-γ1 levels in rats in vivo. The effects of dietary K+ on Bmx were more pronounced in rats fed a high-salt diet compared with rats fed a low-salt diet. These experiments elucidated an endothelial cell signaling mechanism regulated by electrolytes, further demonstrating an integral relationship between endothelial cell function and dietary Na+ and K+ content.

Stable VIP analogue Ro-24-9981 potentiates substance P-induced plasma exudation in hamster cheek pouch

1995 ◽  
Vol 79 (3) ◽  
pp. 968-974 ◽  
Author(s):  
X. P. Gao ◽  
H. A. Jaffe ◽  
C. O. Olopade ◽  
I. Rubinstein
Keyword(s):  
Methyl Ester ◽  
Substance P ◽  
Calcium Ionophore ◽  
Fluorescein Isothiocyanate ◽  
No Synthase ◽  
Cheek Pouch ◽  
Site Formation ◽  
Induced Responses ◽  
Hamster Cheek Pouch ◽  
Plasma Exudation

The purpose of this study was to determine whether vasoactive intestinal peptide (VIP; 300 nM) and a stable cyclic analogue of VIP, Ro-24–9981 (226 nM), modulated neurogenic plasma exudation in the oral cavity in situ and, if so, to determine the mechanisms that mediated these responses. With the use of intravital microscopy, we found that suffusion of substance P induced a significant concentration-dependent formation of fluorescein-isothiocyanate-dextran (mol wt 70 kDa) leaky sites in the hamster cheek pouch (P < 0.05). These effects were significantly and stereospecifically attenuated by NG-nitro-L-arginine methyl ester, an inhibitor of NO synthase, and restored by L-arginine, the substrate for NO synthase (P < 0.05). Topical application of human VIP and Ro-24–9981 had no significant effects of leaky site formation. In addition, human VIP had no significant effects on substance P-induced responses. By contrast, Ro-24–9981 significantly potentiated substance P- and capsaicin-induced leaky site formation (P < 0.05). The effects of Ro-24–9981 on substance P-induced responses were significantly attenuated by NG-nitro-L-arginine methyl ester and restored by L-arginine (P < 0.05). Indomethacin had no significant effects on Ro-24–9981-induced responses. Ro-24–9981 had no significant effects on adenosine- and calcium ionophore A-23187-induced leaky site formation. Collectively, these data suggest that VIP plays no significant role in modulating neurogenic plasma exudation in the oral mucosa. By contrast, Ro-24–9981 amplified this response in a specific receptor-mediated fashion.

scholarly journals Nucleocytoplasmic Trafficking of the Syk Protein Tyrosine Kinase

2006 ◽  
Vol 26 (9) ◽  
pp. 3478-3491 ◽  
Author(s):  
Fei Zhou ◽  
Jianjie Hu ◽  
Haiyan Ma ◽  
Marietta L. Harrison ◽  
Robert L. Geahlen
Keyword(s):  
Oxidative Stress ◽  
Tyrosine Kinase ◽  
Intracellular Signaling ◽  
Protein Tyrosine Kinase ◽  
Caspase 3 ◽  
Catalytic Domain ◽  
Cell Receptor ◽  
Nucleocytoplasmic Trafficking ◽  
Protein Tyrosine ◽  
Syk Protein Tyrosine Kinase

ABSTRACT The protein tyrosine kinase Syk couples the B-cell receptor (BCR) for antigen to multiple intracellular signaling pathways and also modulates cellular responses to inducers of oxidative stress in a receptor-independent fashion. In B cells, Syk is found in both the nuclear and cytoplasmic compartments but contains no recognizable nuclear localization or export signals. Through the analysis of a series of deletion mutants, we identified the presence of an unconventional shuttling sequence near the junction of the catalytic domain and the linker B region that accounts for Syk's subcellular localization. This localization is altered following prolonged engagement of the BCR, which causes Syk to be excluded from the nucleus. Nuclear exclusion requires the receptor-mediated activation of protein kinase C and new protein synthesis. Both of these processes also potentiate the activation of caspase 3 in cells in response to oxidative stress in a manner that is dependent on the localization of Syk outside of the nucleus. In contrast, restriction of Syk to the nucleus greatly diminishes the stress-induced activation of caspase 3.

Involvement of Syk protein tyrosine kinase in LPS-induced responses in macrophages

2007 ◽  
Vol 13 (2) ◽  
pp. 117-125 ◽  
Author(s):  
Marina Ulanova ◽  
Samuel Asfaha ◽  
Grant Stenton ◽  
Alison Lint ◽  
Deanna Gilbertson ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Induced Responses ◽  
Protein Tyrosine ◽  
Syk Protein Tyrosine Kinase
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