cGMP信号传导通路及钙敏感钾通道在D型钠尿肽抑制豚鼠胃动力中的作用  

Effect of cGMP signal pathway and calcium-activated potassium channel on dendroaspis natriuretic peptide-induced inhibition of gastric motility in guinea-pig

作　　者：张曙影[1,2] 蔡正旭[1] 蔡春玉[3] 郭慧淑[1] 

机构地区：[1]大连医科大学附属第一医院,辽宁大连116011 [2]大连大学附属中山医院 [3]延边大学附属医院

出　　处：《山东医药》2010年第25期1-3,共3页Shandong Medical Journal

基　　金：国家自然科学基金资助(NO.30800382);大连市科学发展计划项目(2008E13Sf213)

摘　　要：目的观察豚鼠胃内是否存在钠尿肽(NP)受体,并观察cGMP信号传导通路及钙敏感钾通道在D型钠尿肽(DNP)抑制豚鼠胃动力中的作用。方法用放射自显影技术检测NP受体在胃内的分布,用四道生理记录仪记录胃平滑肌的自发性收缩活动,用膜片钳技术的全细胞技术记录钙敏感钾电流。结果 NP受体存在于豚鼠胃底、胃体和胃窦,并在胃窦部密度最大。DNP抑制胃窦环形肌自发性收缩活动并呈现剂量依赖关系,DNP的这种抑制效应被鸟苷酸环化酶抑制剂LY83583所减弱而被cGMP敏感的磷酸酯酶抑制剂所增强。非选择性钾通道抑制剂四乙胺明显抑制DNP对豚鼠胃窦环形肌自发性收缩活动的抑制作用。10 nmol/L的DNP增加豚鼠胃窦环形肌上钙敏感钾通道。结论 NP受体存在于豚鼠胃内并在胃窦部位分布密度最大,DNP明显抑制豚鼠胃窦环形肌自发性收缩活动,这种抑制效应可能通过cGMP途径实现,并且钙敏感钾通道可能也参与此过程。Objective To determine whether the natriuretic peptide receptor（NPR） presenting in the stomach of guinea pigs and to investigate cGMP signal pathway and calcium-activated potassium channel on dendroaspis natriuretic peptide-induced inhibition of gastric motility in guinea-pig.Methods The distribution of the NPR was analyzed by autoradioimmunography.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 introduced to record calcium-activated potassium currents in the gastric myocytes isolated by collagenase.Results The NPR existed in the gastric fundus,gastric body,and gastric antrum of guinea pigs,and its density was the largest in the gastricantrum.DNP inhibited spontaneous contraction and exhibited a dose-dependent manner.The DNP-induced inhibition was diminished by LY83583（a guanylate cyclase inhibitor） and was potentiated by zaprinast（a cGMP-sensitive phosphoesterase inhibitor）.The inhibitory effect of DNP on spontaneous contraction was also inhibited by tetraethylammonium（a non-selective potassium channel blocker）;10 nmol/L DNP increased the calcium-activated potassium currents in the gastric circular myocytes of guinea pigs.Conclusions The NPR is the most common in the gastric antrum of guinea pigs.DNP significantly inhibits gastric motility in the gastric antrum of guinea pigs.The inhibitory effect occurs via a cGMP-dependent pathway,and a calcium-activated potassium channel may be also involved in the relaxation induced by DNP in gastric antral circular smooth muscles.

关 键 词：D型钠尿肽 钠尿肽受体 胃动力 三磷酸鸟苷 钙敏感钾通道 

分 类 号：R333[医药卫生—人体生理学]