钾通道在D型钠尿肽抑制胃动力中的作用  

Role of potassium channels in Dendroaspis natriuretic peptide-induced inhibition of gastric motility

作　　者：闻庆平[1] 蔡春玉[2] 李萍[1] 蔡正旭[1] 程雷[1] 齐清会[1] 郭慧淑[1] 

机构地区：[1]大连医科大学附属第一医院中心实验室,辽宁省大连市116011 [2]延边大学附属医院内科,吉林省延吉市133000

出　　处：《世界华人消化杂志》2010年第3期217-221,共5页World Chinese Journal of Digestology

基　　金：国家自然科学基金资助项目;No.30800382;No.30572449;大连市科学发展计划资助项目;No.2008E13SF213~~

摘　　要：目的:探讨钾通道在D型钠尿肽抑制豚鼠胃窦环形肌自发性收缩活动中的作用.方法:采用四道生理记录仪记录豚鼠胃窦环形肌自发性收缩活动;应用放射免疫法测定豚鼠胃窦环形肌组织和灌流液中环-磷酸鸟苷(cGMP)含量;运用全细胞模式的膜片钳技术记录豚鼠胃窦环形肌上钙敏感钾电流和延迟整流型钾电流.结果:DNP抑制豚鼠胃窦环形肌自发性收缩活动并呈现剂量依赖性.1、10、100及1000nmol/L的DNP抑制自发性收缩幅度分别为35%±6%、54%±6%、78%±13%及94%±6%.10nmol/L鸟苷酸环化酶抑制剂LY83583使收缩幅度抑制减弱(42%±6%vs60%±4%P<0.05);而用100nmol/L的cGMP依赖的磷酸脂酶抑制剂Zaparinast使DNP对胃窦环行肌自发性收缩的抑制效应增强(72%±7%vs58%±5%,P<0.05).DNP明显增加豚鼠胃窦环形肌组织和灌流液中的cGMP水平.10nmol/LDNP增加豚鼠胃窦环形肌上钙敏感钾电流,在60mV时增加的幅值为62.31%±3.22%,抑制延迟整流型钾电流,在60mV时抑制幅度为18%±2.3%.结论:DNP通过增加IK(Ca)和cGMP途径实现对豚鼠胃窦环形肌的舒张作用.IK(V)不参与此过程,但在维持豚鼠胃窦环形肌细胞的静息膜电位中起重要作用.AIM：To investigate the role of potassium channels in Dendroaspis natriuretic peptide（DNP）-induced relaxation of gastric antral circular smooth muscle of guinea pigs.METHODS：The spontaneous contraction of gastric antral circular muscle of guinea pigs was recorded using a four-channel physiograph.The contents of cyclic guanosine monophosphate（cGMP） in gastric antral smooth muscle tissue and in perfusion medium were measured by radioimmunoassay.The whole cell patch-clamp technique was used to record calcium-activated potassium current（I K（Ca） ） and delayed rectifier potassium current（I K（V） ） in gastric myocytes isolated by collagenase digestion.RESULTS：DNP inhibited the spontaneous contraction of gastric antral circular smooth muscle in a dose-dependent manner.DNP at concentrations of 1, 10, 100 and 1 000 nmol/L reduced the amplitude of the spontaneous contraction by 35% ± 6%, 54% ± 6%, 78% ± 13% and 94% ± 6%, respectively.LY83583, an inhibitor of soluble guanylate cyclase, significantly blocked DNPinduced relaxation of gastric antral circular smooth muscle（reduced amplitude：42% ± 6% vs 60% ± 4%, P 0.05）.In contrast, zaprinast, a cGMP-sensitive phosphodiesterase inhibitor, potentiated DNP-induced relaxation of gastric antral circular smooth muscle（reduced amplitude：72% ± 7% vs 58% ± 5%, P 0.05）.DNP markedly enhanced cGMP levels in gastric antral smooth muscle tissue and in perfusion medium.DNP increased the amplitude of I K（Ca） at 60 mV by 62.31% ± 3.22%, but decreased the amplitude of I K（V） at 60 mV by 18% ± 2.3% in gastric antral circular myocytes of guinea pigs.CONCLUSION：DNP relaxes the gastric antral circular smooth muscle of guinea pigs by increasing I K（Ca） in a cGMP-dependent pathway.I K（V） may play a critical role in regulating resting membrane potential in gastric antral circular myocytes of guinea pigs.

关 键 词：D型钠尿肽 钾通道 环-磷酸鸟苷 胃动力 豚鼠 

分 类 号：R57[医药卫生—消化系统]