Extracellular Nucleotides Can Induce Chemokine (C-C motif) Ligand 2 Expression in Human Vascular Smooth Muscle Cells

To understand the roles of purinergic receptors and cellular molecules below the receptors in the vascular inflammatory response, we determined if extracellular nucleotides up-regulated chemokine expression in vascular smooth muscle cells (VSMCs). Human aortic smooth muscle cells (AoSMCs) abundantly express P2Y1, P2Y6, and P2Y11 receptors, which all respond to extracellular nucleotides. Exposure of human AoSMCs to NAD+ , an agonist of the human P2Y11 receptor, and NADP+ as well as ATP, an agonist for P2Y1 and P2Y11 receptors, caused increase in chemokine (C-C motif) ligand 2 gene (CCL2) transcript and CCL2 release; however, UPT did not affect CCL2 expression. CCL2 release by NAD+ and NADP+ was inhibited by a concentration dependent manner by suramin, an antagonist of P2-purinergic receptors. NAD+ and NADP+ activated protein kinase C and enhanced phosphorylation of mitogen-activated protein kinases and Akt. NAD(+)- and NADP(+)-mediated CCL2 release was significantly attenuated by SP6001250, U0126, LY294002, Akt inhibitor IV, RO318220, GF109203X, and diphenyleneiodium chloride. These results indicate that extracellular nucleotides can promote the proinflammatory VSMC phenotype by up-regulating CCL2 expression, and that multiple cellular elements, including phosphatidylinositol 3-kinase, Akt, protein kinase C, and mitogen-activated protein kinases, are involved in that process.

Function of P2 receptors in skeletal muscle and their roles in the diseases / 中国药理学通报

P2 receptors activated by purine and pyrimidine nucleotides are divided into two subclasses:P2Y receptors which are G-protein coupled and P2X receptors which are ligand-gated ion channels.The expression of specific P2X and P2Y receptor subtypes in skeletal muscle cells has been demonstrated.Purinergic signaling plays an important role in muscle regeneration of muscular dystrophy,and is involved in skeletal muscle diseases such as muscular dystrophy,tendon inflammation and epilepsy,and provides the possibility of new therapeutic strategies for the treatment of muscle diseases.

P2 receptors in blood vessel and its relationship with some vascular diseases / 基础医学与临床

P2 receptors are divided into two subclasses:P2X receptors which are ligand-gated ion channels and P2Y receptors which are G-protein coupled. Several kinds of P2X and P2Y receptor subtypes express in vascular endo-thelial cells and vascular smooth muscle cells. Purinergic signalling plays an important role in vascular diseases such as atherosclerosis, cerebral vessels ageing and blood vessel remodeling. So this signalling pathway may pro-vide a new target to treat vascular diseases.

P2 receptors in blood vessel and its relationship with some vascular diseases / 基础医学与临床

P2 receptors are divided into two subclasses:P2X receptors which are ligand-gated ion channels and P2Y receptors which are G-protein coupled.Several kinds of P2X and P2Y receptor subtypes express in vascular endothelial cells and vascular smooth muscle cells.Purinergic signalling plays an important role in vascular diseases such as atherosclerosis,cerebral vessels ageing and blood vessel remodeling.So this signalling pathway may provide a new target to treat vascular diseases.