Abstract
Aim:
To test whether carbachol can influence endothelial barrier dysfunction induced by tumor necrosis factor (TNF)-α and whether the alpha 7 nicotinic receptor can mediate this process.
Methods:
Rat cardiac microvascular endothelial cells were exposed to carbachol followed by TNF-α treatment in the presence or the absence of α-bungarotoxin (an antagonist of the alpha 7 nicotinic receptor). Permeability of endothelial cells cultured on Transwell filters was assayed using FITC-albumin. F-actin was stained with FITC- phalloidin. Expression of vascular endothelial cadherin, intercellular adhesion molecule 1 (ICAM-1), phosphor-ERK1/2 and phosphor-JNK was detected using Western blot.
Results:
Carbachol (2 μmol/L-2 mmol/L) prevented increase in endothelial cell permeability induced by TNF-α (500 ng/mL) in a dose-dependent manner. Further, it attenuated the down-regulation of vascular endothelial cadherin and the up-regulation of ICAM-1 induced by TNF-α. In addition, treatment of endothelial cells with carbachol decreased phosphor-ERK1/2 and phosphor-JNK. These effects of carbachol were blocked by α-bungarotoxin 3 μg/mL.
Conclusion:
These data suggest that the inhibitory effect of carbachol on TNF-α-induced endothelial barrier dysfunction mediated by the alpha 7 nicotinic receptor.
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Acknowledgements
This work was supported by the Special Foundation of the 11th Five-Year Plan for Military Medical Project (No 06Z055).
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Li, Yz., Liu, Xh., Rong, F. et al. Carbachol inhibits TNF-α-induced endothelial barrier dysfunction through alpha 7 nicotinic receptors. Acta Pharmacol Sin 31, 1389–1394 (2010). https://doi.org/10.1038/aps.2010.165
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DOI: https://doi.org/10.1038/aps.2010.165
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