Objective To determine whether matrine, a kind of traditional Chinese medicinal alkaloid, can relax the aortic smooth muscles isolated from guinea pigs and to investigate the mechanism of its relaxant effects. Methods...Objective To determine whether matrine, a kind of traditional Chinese medicinal alkaloid, can relax the aortic smooth muscles isolated from guinea pigs and to investigate the mechanism of its relaxant effects. Methods Phenylephrine or potassium chloride concentration-dependent relaxation response of aortic smooth muscles to matrine was studied in the precontracted guinea pigs. Results Matrine （1×10^-4 mol/L -3.3×10^-3 mol/L） relaxed the endothelium-denuded aortic rings pre-contracted sub-maximally with phenylephrine, in a concentration-dependent manner, and its pre-incubation （3.3× 10^- 3 mol/L） produced a significant rightward shift in the phenylephrine dose-response curve, but had no effects on the potassium chloride-induced contraction. The anti-contractile effect of matrine was not reduced by the highly selective ATP-dependent K^＋ channel blocker glibenclamide （10.5 mol/L）, either by the non-selective K^＋channel blocker tetraethylammonium （10^-3 mol/L）, or by the β-antagonist propranolol （10^-5 mol/L）. In either ＂normal＂ or ＂Ca^2＋-free＂ bathing medium, the phenylephrine-induced contraction was attenuated by matrine （3.3×10^-3 mol/L）, indicating that the vasorelaxation was due to inhibition of intracellular and extracellular Ca^2＋ mobilization. Conclusion Matrine inhibits phenylephrine-induced contractions by inhibiting activation of α-adrenoceptor and interfering with the release of intracellular Ca^2＋ and the influx of extracellular Ca^2＋.展开更多
AIM:To investigate the relaxant effect of chromane HEF-19 on colonic smooth muscles isolated from rabbits,and the underlying mechanisms.METHODS:The relaxant effect and action mechanisms of HEF-19 were investigated usi...AIM:To investigate the relaxant effect of chromane HEF-19 on colonic smooth muscles isolated from rabbits,and the underlying mechanisms.METHODS:The relaxant effect and action mechanisms of HEF-19 were investigated using descending colon smooth muscle of the rabbits.Preparations 1 cm long were mounted in 15-mL tissue baths containing Tyrode’s solution,maintained at 37±0.5℃and aerated with a mixture of 5%CO2in oxygen(Carbogen).The tension and amplitude of the smooth muscle strips were recorded after adding HEF-19(10-6,10-5and 10-4mol/L).After cumulative administration of four antispasmodic agents,including acetylcholine chloride(Ach)(10-4mol/L),histamine(10-4mol/L),high-K+(60 mmol/L)and BaCl2(8.2 mmol/L),HEF-19(3×10-7-3×10-4mol/L)was added to investigate the relaxant effect of HEF-19.CaCl2(10-4-2.5×10-3mol/L)was added cumulatively to the smooth muscle preparations pretreated with and without HEF-19(1×10-6or 3×10-6mol/L)and verapamil(1×10-7mol/L)to study the mechanisms involved.Finally,phasic contraction was induced with ACh(15×10-6mol/L),and CaCl2(4×10-3mol/L)was added to the smooth muscle preparations pretreated with and without HEF-19(3×10-6mol/L or 1×10-5mol/L)and verapamil(1×10-7mol/L)in calcium-free medium to further study the underlying mechanisms.RESULTS:HEF-19(1×10-6,1×10-5and 1×10-4mol/L)suppressed spontaneous contraction of rabbit colonic smooth muscles.HEF-19(3×10-7-3×10-4mol/L)relaxed in a concentration-dependent manner colonic smooth muscle preparations pre-contracted with BaCl2,high-K+solution,Ach or histamine with respective EC50values of 5.15±0.05,5.12±0.08,5.58±0.16and 5.25±0.24,thus showing a spasmolytic activity.HEF-19(1×10-6mol/L and 3×10-6mol/L)shifted the concentration-response curves of CaCl2to the right and depressed the maximum response to CaCl2.The two components contracted by Ach were attenuated with HEF-19(3×10-6mol/L or 10-5mol/L)in calcium-free medium.CONCLUSION:HEF-19 inhibited rabbit colonic smooth muscle contraction,probably through inhibiting opening of 展开更多
肠道平滑肌的收缩和舒张与粗细肌丝的调节密切相关。Caldesmon作为一种肌动蛋白结合蛋白,是参与肠道平滑肌粗细肌丝调节的重要收缩蛋白之一,可通过与肌动蛋白、肌球蛋白和原肌球蛋白交联,阻碍肌动蛋白与肌球蛋白的结合,从而抑制肠道平...肠道平滑肌的收缩和舒张与粗细肌丝的调节密切相关。Caldesmon作为一种肌动蛋白结合蛋白,是参与肠道平滑肌粗细肌丝调节的重要收缩蛋白之一,可通过与肌动蛋白、肌球蛋白和原肌球蛋白交联,阻碍肌动蛋白与肌球蛋白的结合,从而抑制肠道平滑肌的收缩。然而,Caldesmon的磷酸化修饰可以逆转这种抑制作用。Caldesmon可以被不同信号通路中的蛋白激酶刺激,引起自身的磷酸化,促进肌动蛋白与肌球蛋白的结合,进一步导致肠道平滑肌的收缩,在肠道动力障碍疾病中起到关键作用。分别以“Caldesmon”、“平滑肌”、“磷酸化”和以“Caldesmon”、“smooth muscle”、“phosphorylation”、“actin”、“myosin”、“contraction and relaxation”为主题词在中国知网(CNKI)、百度学术和PubMed数据库中查找Caldesmon与平滑肌或肠道平滑肌相关文献。该文就Caldesmon及其磷酸化参与调节肠道平滑肌收缩舒张的功能以及介导Caldesmon磷酸化的相关上游信号通路等方面进行综述,旨在为以基于Caldesmon及其磷酸化调节肠道平滑肌收缩舒张为靶点的临床疾病治疗提供理论依据。展开更多
基金supported by the Program for New Century Excellent Talents in Universities of the Ministry of Education of China (NCET-06-0916)Ningxia Natural Science Foundation (NZ0782)Ningxia Academic Scientific Research Program (2005-2007)
文摘Objective To determine whether matrine, a kind of traditional Chinese medicinal alkaloid, can relax the aortic smooth muscles isolated from guinea pigs and to investigate the mechanism of its relaxant effects. Methods Phenylephrine or potassium chloride concentration-dependent relaxation response of aortic smooth muscles to matrine was studied in the precontracted guinea pigs. Results Matrine （1×10^-4 mol/L -3.3×10^-3 mol/L） relaxed the endothelium-denuded aortic rings pre-contracted sub-maximally with phenylephrine, in a concentration-dependent manner, and its pre-incubation （3.3× 10^- 3 mol/L） produced a significant rightward shift in the phenylephrine dose-response curve, but had no effects on the potassium chloride-induced contraction. The anti-contractile effect of matrine was not reduced by the highly selective ATP-dependent K^＋ channel blocker glibenclamide （10.5 mol/L）, either by the non-selective K^＋channel blocker tetraethylammonium （10^-3 mol/L）, or by the β-antagonist propranolol （10^-5 mol/L）. In either ＂normal＂ or ＂Ca^2＋-free＂ bathing medium, the phenylephrine-induced contraction was attenuated by matrine （3.3×10^-3 mol/L）, indicating that the vasorelaxation was due to inhibition of intracellular and extracellular Ca^2＋ mobilization. Conclusion Matrine inhibits phenylephrine-induced contractions by inhibiting activation of α-adrenoceptor and interfering with the release of intracellular Ca^2＋ and the influx of extracellular Ca^2＋.
文摘AIM:To investigate the relaxant effect of chromane HEF-19 on colonic smooth muscles isolated from rabbits,and the underlying mechanisms.METHODS:The relaxant effect and action mechanisms of HEF-19 were investigated using descending colon smooth muscle of the rabbits.Preparations 1 cm long were mounted in 15-mL tissue baths containing Tyrode’s solution,maintained at 37±0.5℃and aerated with a mixture of 5%CO2in oxygen(Carbogen).The tension and amplitude of the smooth muscle strips were recorded after adding HEF-19(10-6,10-5and 10-4mol/L).After cumulative administration of four antispasmodic agents,including acetylcholine chloride(Ach)(10-4mol/L),histamine(10-4mol/L),high-K+(60 mmol/L)and BaCl2(8.2 mmol/L),HEF-19(3×10-7-3×10-4mol/L)was added to investigate the relaxant effect of HEF-19.CaCl2(10-4-2.5×10-3mol/L)was added cumulatively to the smooth muscle preparations pretreated with and without HEF-19(1×10-6or 3×10-6mol/L)and verapamil(1×10-7mol/L)to study the mechanisms involved.Finally,phasic contraction was induced with ACh(15×10-6mol/L),and CaCl2(4×10-3mol/L)was added to the smooth muscle preparations pretreated with and without HEF-19(3×10-6mol/L or 1×10-5mol/L)and verapamil(1×10-7mol/L)in calcium-free medium to further study the underlying mechanisms.RESULTS:HEF-19(1×10-6,1×10-5and 1×10-4mol/L)suppressed spontaneous contraction of rabbit colonic smooth muscles.HEF-19(3×10-7-3×10-4mol/L)relaxed in a concentration-dependent manner colonic smooth muscle preparations pre-contracted with BaCl2,high-K+solution,Ach or histamine with respective EC50values of 5.15±0.05,5.12±0.08,5.58±0.16and 5.25±0.24,thus showing a spasmolytic activity.HEF-19(1×10-6mol/L and 3×10-6mol/L)shifted the concentration-response curves of CaCl2to the right and depressed the maximum response to CaCl2.The two components contracted by Ach were attenuated with HEF-19(3×10-6mol/L or 10-5mol/L)in calcium-free medium.CONCLUSION:HEF-19 inhibited rabbit colonic smooth muscle contraction,probably through inhibiting opening of
文摘肠道平滑肌的收缩和舒张与粗细肌丝的调节密切相关。Caldesmon作为一种肌动蛋白结合蛋白,是参与肠道平滑肌粗细肌丝调节的重要收缩蛋白之一,可通过与肌动蛋白、肌球蛋白和原肌球蛋白交联,阻碍肌动蛋白与肌球蛋白的结合,从而抑制肠道平滑肌的收缩。然而,Caldesmon的磷酸化修饰可以逆转这种抑制作用。Caldesmon可以被不同信号通路中的蛋白激酶刺激,引起自身的磷酸化,促进肌动蛋白与肌球蛋白的结合,进一步导致肠道平滑肌的收缩,在肠道动力障碍疾病中起到关键作用。分别以“Caldesmon”、“平滑肌”、“磷酸化”和以“Caldesmon”、“smooth muscle”、“phosphorylation”、“actin”、“myosin”、“contraction and relaxation”为主题词在中国知网(CNKI)、百度学术和PubMed数据库中查找Caldesmon与平滑肌或肠道平滑肌相关文献。该文就Caldesmon及其磷酸化参与调节肠道平滑肌收缩舒张的功能以及介导Caldesmon磷酸化的相关上游信号通路等方面进行综述,旨在为以基于Caldesmon及其磷酸化调节肠道平滑肌收缩舒张为靶点的临床疾病治疗提供理论依据。
