Carbachol inhibits TNF-α-induced endothelial barrier dysfunction through alpha 7 nicotinic receptors  

作　　者：Yu-zhen LI Xiu-hua LIU Fei RONG Sen HU Zhi-yong SHENG 

机构地区：[1]Department of Pathophysiology, Chinese PLA General Hospital, Beijing 100853, China [2]Laboratory of Shock and Multiple Organ Dysfunction, Burns Institute, the First Affiliated Hospital of PLA General Hospital, Beijing 100037, China

出　　处：《Acta Pharmacologica Sinica》2010年第10期1389-1394,共6页中国药理学报（英文版）

摘　　要：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 pmol/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 pg/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.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 pmol/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 pg/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.

关 键 词：CARBACHOL alpha 7 nicotinic receptors ENDOTHELIUM barrier function tumor necrosis factor α intercellular adhesion molecule 1 ERK1/2 

分 类 号：Q253[生物学—细胞生物学] Q425