Back to Search
Start Over
Transient and Prolonged Increase in Endothelial Permeability Induced by Histamine and Thrombin
- Source :
- Circulation Research. 83:1115-1123
- Publication Year :
- 1998
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 1998.
-
Abstract
- Abstract —In the present study, we differentiated between short- and long-term effects of vasoactive compounds on human endothelial permeability in an in vitro model. Histamine induced a rapid and transient (22 Na ions. This increase in permeability was inhibited completely by chelation of intracellular calcium ions by BAPTA-AM and inhibition of calmodulin activity and myosin light chain (MLC) phosphorylation. The presence of serum factors prolonged the barrier dysfunction induced by histamine. Thrombin by itself induced a prolonged barrier dysfunction (>30 minutes) as evidenced by an increased passage of peroxidase and 40 kDa dextran. It was dependent only partially on calcium ions and calmodulin. The protein tyrosine kinase inhibitors genistein and herbimycin A, but not the inactive analogue daidzein, inhibited to a large extent the increase in permeability induced by thrombin. Genistein and BAPTA-AM inhibited the thrombin-induced permeability in an additive way, causing together an almost complete prevention of the thrombin-induced increase in permeability. Inhibition of protein tyrosine kinase was accompanied by a decrease in MLC phosphorylation and a reduction in the extent of F-actin fiber and focal attachment formation. Inhibition of Rho A by C3 transferase toxin reduced both the thrombin-induced barrier dysfunction and MLC phosphorylation. Genistein and C3 transferase toxin did not elevate the cellular cAMP levels. No evidence was found for a significant role of protein kinase C in the thrombin-induced increase in permeability or in the accompanying MLC phosphorylation. These data indicate that in endothelial cell monolayers that respond to histamine in a physiological way, thrombin induces a prolonged increase in permeability by “calcium sensitization,” which involves protein tyrosine phosphorylation and Rho A activation.
- Subjects :
- Time Factors
RHOA
Physiology
Vascular permeability
Biology
Capillary Permeability
chemistry.chemical_compound
Thrombin
BAPTA
GTP-Binding Proteins
medicine
Humans
Cells, Cultured
Cytoskeleton
Protein kinase C
Infant, Newborn
Tyrosine phosphorylation
Protein-Tyrosine Kinases
Molecular biology
Cell biology
chemistry
biology.protein
Phosphorylation
Calcium
Endothelium, Vascular
rhoA GTP-Binding Protein
Cardiology and Cardiovascular Medicine
Protein Kinases
Tyrosine kinase
Histamine
medicine.drug
Subjects
Details
- ISSN :
- 15244571 and 00097330
- Volume :
- 83
- Database :
- OpenAIRE
- Journal :
- Circulation Research
- Accession number :
- edsair.doi.dedup.....715f304c3ad1fa5cf963b75b88393f60