【摘要】 目的探讨L-型钙通道电流在D型钠尿肽(DNP)抑制豚鼠胃动力中的作用及机制。方法制作豚鼠胃窦部环形肌肌条后,用多道生理记录仪记录环形肌自发性收缩活动;分离环形肌细胞后,用膜片钳记录细胞L-型钡电流(IBa),以IBa代表钙电流;观察不同抑制剂预处理后,10 nmol/L DNP对IBa的影响。结果 1、10、100 nmol/LDNP抑制豚鼠胃窦环形肌自发性收缩的幅度分别为(35.00±7.00)%、(54.00±8.00)%、(78.00±13.00)%,呈明显的剂量依赖性(r=0.923,P<0.05)。1、10、100 nmol/L DNP抑制豚鼠胃窦环形肌细胞上IBa分别为(60.12±2.02)%、(57.12±3.02)%、(42.12±3.16)%。用鸟苷酸环化酶抑制剂LY83583预处理后,10 nmol/L DNP对IBa的抑制作用由预处理前的(67.12±4.02)%减弱为(88.03±4.15)%;用cGMP依赖的蛋白激酶G抑制剂KT5823预处理后,几乎完全阻断了10 nmol/L DNP引起的IBa抑制作用;而用cGMP敏感的磷酸酯酶抑制剂zaparinast预处理后,10 nmol/L DNP对IBa的抑制作用由预处理前的(67.12±4.02)%增强至(53.00±4.23)%。结论 DNP能明显抑制豚鼠胃窦环形肌自发性收缩,其作用机制可能与pGC-cGMP-PKG通路有关。更多还原

【Abstract】 Objective To investigate the role of L-type calcium current in DNP-induced inhibition of gastric motility and its mechanism in gastric antral myocytes of guinea pigs.Methods The spontaneous contraction of gastric antral circular muscles of guinea pigs was recorded by a 4-channel physiograph.The whole-cell patch-clamp technique was used to record IBa as L-type calcium channel currents.Results DNP inhibited spontaneous contraction and exhibited a dose-dependent manner at the concentrations of 1 nmol/L,10 nmol/L and 100 nmol/L,DNP inhibited spontaneous contraction(35.00±7.00)%,(54.00±8.00)%,(78.00±13.00)%;DNP suppressed IBa in a dose-dependant manner at the concentrations of 1 nmol/L,10 nmol/L and 100 nmol/L,DNP inhibited IBa to(60.12±2.02)%,(57.12±3.02)%,and(42.12±3.16)%,respectively in gastric antral circular smooth muscle cells(SMCs) of guinea pigs.DNP-induced inhibition of IBa was partially blocked by LY83583,an inhibitor of guanylate cyclase,the inhibited amplitude from(67.12±4.02) % to(88.03±4.15) %.KT5823,a cGMP-dependent protein kinase(PKG) inhibitor,almost completely blocked DNP-induced inhibition of IBa.However,DNP-induced inhibition of IBa was potentiated by zaprinast,an inhibitor of cGMP-sensitive phosphodiesterase,the inhibited amplitude from(67.12±4.02)% to(53.00±4.23)%.Conclusions DNP significantly inhibits gastric motility in the gastric antrum of guinea pigs.DNP inhibits L-type calcium channel currents via pGC-cGMP-PKG-dependent signal pathway in gastric antral myocytes of guinea pigs.更多还原