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Comprehensive study of rutaecarpine on vascular constriction relative to RhoA/MLCP-MLC signaling

吴茱萸次碱对血管收缩及RhoA/MLCP-MLC信号通路的影响(英文)
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摘要 The aims of the present study are to investigate the effect of vasoconstriction and to explore the mechanism of rutae- carpine. The research findings showed that rutaecarpine could induce contractions of the rat thoracic aorta in vitro. The inhibitors of Rho-kinase and inositol 1,4,5-triphosphate receptor (IP 3 R) could suppress the effect of rutaecarpine-induced vasoconstriction. In the study of A7r5 cells (a line of smooth muscle cells), 300 μg/L rutaecarpine promoted the concentration of intracellular Ca 2+ and enhanced the IP 3 R expression, which connects with 1,4,5-triphosphate to evoke the release of Ca 2+ from the intracellular stores. Rutaecarpine increased the RhoA mRNA expression when the cells were pretreated with inhibitor H-1152, and improved the levels of phosphorylation of myosin light chain phosphatase (MLCP) and myosin light chain (MLC). These results suggest that rutaecarpine plays a role in vasoconstriction relative to the RhoA/MLCP-MLC signaling pathway, which denotes a new field of rutaecarpine in pharmacology. 本文对吴茱萸次碱的收缩血管效应及其机制进行了研究。结果表明,吴茱萸次碱体外可明显的引起大鼠胸主动脉血管平滑肌收缩。与血管平滑肌收缩相关的信号蛋白Rho激酶(RhoA)和IP3受体(IP3R)的抑制剂可以抑制吴茱萸次碱的缩血管效应。血管平滑肌细胞A7r5的实验发现,吴茱萸次碱(300μg/L)可以明显升高胞内Ca2+浓度,促进IP3R的mRNA表达,而后者与胞内Ca2+浓度升高有关。预先使用RhoA抑制剂H-1152,吴茱萸次碱仍能使RhoA mRNA表达升高。此外,吴茱萸次碱能够促进肌球蛋白轻链磷酸酶(MLCP)以及肌球蛋白轻链(MLC)的磷酸化。提示吴茱萸次碱的缩血管效应与RhoA/MLCP-MLC信号转导通路有关。本工作对于深入认识吴茱萸次碱的药理活性具有重要的意义。
出处 《Journal of Chinese Pharmaceutical Sciences》 CAS 2012年第5期436-447,共12页 中国药学(英文版)
基金 National Natural Science Foundation of China (Grant No.30801523,30973896,and 81073092) the Projects of Science Research for the 11th Five-Year Plan of the Ministry of Science and Technology of China (Grant No.2006BAI08B03-09) the China's Post-Doctoral Science Fund (Grant No.20080440418) the National S&T Major Special Project for New Drug R&D of China (Grant No.2012ZX09102-201-008,2012ZX09103-201-041and2011ZX09101-002-11)
关键词 RUTAECARPINE Blood vessel Myosin light chain 吴茱萸次碱 血管 肌球蛋白轻链
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