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D型钠尿肽对豚鼠胃窦环形肌细胞钙敏感钾电流的影响及其作用机制
  • 期刊名称:大连医科大学学报
  • 时间:0
  • 页码:1-5
  • 语言:中文
  • 分类:R318[医药卫生—生物医学工程;医药卫生—基础医学]
  • 作者机构:[1]大连医科大学附属第一医院,辽宁大连116011
  • 相关基金:国家自然科学基金资助项目(30800382).
  • 相关项目:D型钠尿肽抑制胃动力的相关机制研究
中文摘要:

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,10nmol/LDNP对IBa的影响。结果1、10、100nmol/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、100nmol/LDNP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,10nmoL/LDNP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10nmol/LDNP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,10nmol/LDNP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。

英文摘要:

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 d-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-de- pendent 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 curents via pGC-cGMP-PKG-dependent signal pathway in gastric antral myocytes of guinea pigs.

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