COX-mediated endothelium-dependent contractions： from the past to recent discoveries  

作　　者：Michael Sze-Ka WONG Paul Michel VANHOUTTE 

机构地区：[1]Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China

出　　处：《Acta Pharmacologica Sinica》2010年第9期1095-1102,共8页中国药理学报（英文版）

摘　　要：Endothelial cells release various substances to control the tone of the underlying vascular smooth muscle. Nitric oxide （NO） is the best defined endothelium-derived relaxing factor （EDRF）. Endothelial cells can also increase vascular tone by releasing endothelium-derived contracting factors （EDCF）. The over-production of EDCF contributes to the endothelial dysfunctions which accompanies various vascular diseases. The present review summarizes and discusses the mechanisms leading to the release of EDCFs derived from the metabolism of arachidonic acid. This release can be triggered by agonists such as acetylcholine, adenosine nucleotides or by stretch. All these stimuli are able to induce calcium influx into the endothelial cells, an effect which can be mimicked by calcium ionophores. The augmentation in intracellular calcium ion concentration initiates the release of EDCF. Downstream processes include activation of phospholipase A2 （PLA2）, cyclooxygenases （COX） and the production of reactive oxygen species （ROS） and vasoconstrictor prostanoids （endoperoxides, prostacyclin, thromboxane A2 and other prostaglandins） which subsequently diffuse to, and activate thromboxaneprostanoid （TP） receptors on the vascular smooth muscle cells leading to contraction.Endothelial cells release various substances to control the tone of the underlying vascular smooth muscle. Nitric oxide （NO） is the best defined endothelium-derived relaxing factor （EDRF）. Endothelial cells can also increase vascular tone by releasing endothelium-derived contracting factors （EDCF）. The over-production of EDCF contributes to the endothelial dysfunctions which accompanies various vascular diseases. The present review summarizes and discusses the mechanisms leading to the release of EDCFs derived from the metabolism of arachidonic acid. This release can be triggered by agonists such as acetylcholine, adenosine nucleotides or by stretch. All these stimuli are able to induce calcium influx into the endothelial cells, an effect which can be mimicked by calcium ionophores. The augmentation in intracellular calcium ion concentration initiates the release of EDCF. Downstream processes include activation of phospholipase A2 （PLA2）, cyclooxygenases （COX） and the production of reactive oxygen species （ROS） and vasoconstrictor prostanoids （endoperoxides, prostacyclin, thromboxane A2 and other prostaglandins） which subsequently diffuse to, and activate thromboxaneprostanoid （TP） receptors on the vascular smooth muscle cells leading to contraction.

关 键 词：CYCLOOXYGENASE EDCF ENDOTHELIUM gap junctions phospholipase A2 PROSTANOIDS reactive oxygen species TP-receptors 

分 类 号：Q25[生物学—细胞生物学] Q463