目的探讨高浓度葡萄糖(简称高糖)对C型钠尿肽(CNP)致胃窦环形肌舒张的影响及其可能机制。方法取大鼠40只制备胃窦环形肌条,肌条收缩活动稳定后,对照1、2组分别加入不同浓度CNP(1×10-8、3×10-8、1×10-7mol/L)及硝普钠(SNP...目的探讨高浓度葡萄糖(简称高糖)对C型钠尿肽(CNP)致胃窦环形肌舒张的影响及其可能机制。方法取大鼠40只制备胃窦环形肌条,肌条收缩活动稳定后,对照1、2组分别加入不同浓度CNP(1×10-8、3×10-8、1×10-7mol/L)及硝普钠(SNP)(1×10-7、3×10-7、1×10-6mol/L),观察其效应,每次加药观察20 m in,冲洗3次;高糖1、2组预加葡萄糖使浴槽终浓度为30 mmol/L,其后操作同对照1、2组;甘露醇组预加甘露醇30mmol/L,其后操作同对照1组;均采用多道生理信号采集处理系统计算CNP(SNP)致平滑肌张力的抑制率。结果对照1、2组产生浓度依赖的胃窦环形肌平滑肌舒张效应,高糖1组可明显抑制CNP和硝普钠产生的平滑肌条舒张效应明显减弱;甘露醇(30 mmol/L)组CNP产生的平滑肌条舒张效应明显减弱。结论高糖抑制CNP引起的胃窦环形肌舒张效应;该效应可能与细胞内外渗透压改变有关。展开更多
AIM: To investigate ion channel mechanism in CNP-induced relaxation of gastric circular smooth muscle in guinea pigs.METHODS: Spontaneous contraction of gastric smooth muscle was recorded by a four -channel physiograp...AIM: To investigate ion channel mechanism in CNP-induced relaxation of gastric circular smooth muscle in guinea pigs.METHODS: Spontaneous contraction of gastric smooth muscle was recorded by a four -channel physiograph. The whole cell patch-clamp technique was used to record calciumactivated potassium currents and membrane potential in the gastric myocytes isolated by collagenase.RESULTS: C-type natriuretic peptide (CNP) markedly inhibited the spontaneous contraction in a dose-dependent manner in gastric circular smooth muscle in guinea pigs.Ly83583, an inhibitor of guanylate cyclase, weakened CNPinduced inhibition on spontaneous contraction but Zaparinast, an inhibitor of cGMP sensitive phosphoesterase,potentiated CNP-induced inhibition in gastric circular smooth muscles. The inhibitory effects of CNP on spontaneous contraction were blocked by tetrathylammonium (TEA), a nonselective potassium channel blocker. CNP hyperpolarized membrane potential from -60.0 mV±2.0 mV to -68.3 meV±3.0 mV in a single gastric myocyte. CNP increased calcium-activated potassium currents (Ik(ca)) in a dose-dependent manner in gastric circular myocytes. CNP also increased the spontaneously transient outward currents (STOCs). Ly83583 partly blocked CNP-induced increase of calcium-activated potassium currents, but Zaparinast potented the effect.CONCLUSION: CNP inhibits spontaneous contraction, and potassium channel may be involved in the process in gastric circular smooth musde of guinea pigs. CNP-induced increase of Ik(ca) is mediated by a cGMP dependent pathway.展开更多
文摘目的探讨高浓度葡萄糖(简称高糖)对C型钠尿肽(CNP)致胃窦环形肌舒张的影响及其可能机制。方法取大鼠40只制备胃窦环形肌条,肌条收缩活动稳定后,对照1、2组分别加入不同浓度CNP(1×10-8、3×10-8、1×10-7mol/L)及硝普钠(SNP)(1×10-7、3×10-7、1×10-6mol/L),观察其效应,每次加药观察20 m in,冲洗3次;高糖1、2组预加葡萄糖使浴槽终浓度为30 mmol/L,其后操作同对照1、2组;甘露醇组预加甘露醇30mmol/L,其后操作同对照1组;均采用多道生理信号采集处理系统计算CNP(SNP)致平滑肌张力的抑制率。结果对照1、2组产生浓度依赖的胃窦环形肌平滑肌舒张效应,高糖1组可明显抑制CNP和硝普钠产生的平滑肌条舒张效应明显减弱;甘露醇(30 mmol/L)组CNP产生的平滑肌条舒张效应明显减弱。结论高糖抑制CNP引起的胃窦环形肌舒张效应;该效应可能与细胞内外渗透压改变有关。
基金the National Natural Science Foundation of China, No.30160028
文摘AIM: To investigate ion channel mechanism in CNP-induced relaxation of gastric circular smooth muscle in guinea pigs.METHODS: Spontaneous contraction of gastric smooth muscle was recorded by a four -channel physiograph. The whole cell patch-clamp technique was used to record calciumactivated potassium currents and membrane potential in the gastric myocytes isolated by collagenase.RESULTS: C-type natriuretic peptide (CNP) markedly inhibited the spontaneous contraction in a dose-dependent manner in gastric circular smooth muscle in guinea pigs.Ly83583, an inhibitor of guanylate cyclase, weakened CNPinduced inhibition on spontaneous contraction but Zaparinast, an inhibitor of cGMP sensitive phosphoesterase,potentiated CNP-induced inhibition in gastric circular smooth muscles. The inhibitory effects of CNP on spontaneous contraction were blocked by tetrathylammonium (TEA), a nonselective potassium channel blocker. CNP hyperpolarized membrane potential from -60.0 mV±2.0 mV to -68.3 meV±3.0 mV in a single gastric myocyte. CNP increased calcium-activated potassium currents (Ik(ca)) in a dose-dependent manner in gastric circular myocytes. CNP also increased the spontaneously transient outward currents (STOCs). Ly83583 partly blocked CNP-induced increase of calcium-activated potassium currents, but Zaparinast potented the effect.CONCLUSION: CNP inhibits spontaneous contraction, and potassium channel may be involved in the process in gastric circular smooth musde of guinea pigs. CNP-induced increase of Ik(ca) is mediated by a cGMP dependent pathway.
