Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3701_Библиотеки_им_академика_М_И_Перельмана

tion of phospholipase C-β, resulting in the formation of inositol-1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 binds to their corresponding receptors which is inositol trisphosphate receptors (IP3Rs) in the sarcoplasmic reticulum; the intracel­lular Ca2+ store. Activation of IP3Rs resulting in efflux of Ca2+ into the cytoplasm. On other hand, DAG activates protein kinase C (PKC), promoting Ca2+ influx via enhancing the vascular channels activity such as voltage-dependent L-type Ca2+ channels. Elevated intracellular Ca2+ concentration [Ca2+]i binds to calmodulin, creating Ca2+-calmodulin complex which activate MLC kinase (MLCK) followed by phosphorylation of contractile proteins that promote myosin-actin filament interac­tions and consequently smooth muscle contraction [6–11]. Contraction of vascular smooth muscle cells could persist via regulation of MLC phosphatase (MLCP). Vasoactive peptides also regulate the dephosphorylation of MLC phosphatase via dif­ferent mechanisms. They utilize the PLC-DAG-PKC pathway, which in turn inhibits phosphatase activity and thus stimulates persistent contraction [12]. In addition, they activate RhoA-Rho kinase pathway, which phosphorylates MLCP and inhibits its activity [13, 14]. On the other hand, a low [Ca2+]i concentration and increased activity of MLC phosphatase promoting vascular smooth muscle cell relaxation [15]. Gαs-coupled GPCR mediated blood vessel relaxation. Adrenaline, as vasodilator, acts on corresponding receptors, recruiting Gαs to stimulate adenylyl cyclase (AC), leading to the formation of cAMP and then activation of protein kinase A (PKA). PKA plays important role in decreasing [Ca2+]i concentrations via phosphorylation of MLCK. This results in activation of calcium pumps in the plasma membrane and sarcoplas­mic reticulum. Furthermore, promotes cell hyperpolarization by opening K+ channels promoting relaxation of vascular smooth muscle cells [8, 16, 17].