权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Intrarenal actions of atrial natriuretic peptides

心房钠尿肽的肾内作用

基本信息

批准号：
61570094
负责人：
ENDOU Hitoshi
金额：
$ 1.34万
依托单位：
University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1986
资助国家：
日本
起止时间：
1986 至 1987
项目状态：
已结题

项目摘要

Although atrial extracts and newly synthesized atrial natriuretic peptides (ANP) reveal a strong natriuretic effect, their intrarenal sites of action have not been clarified yet. This study was designed, therefore, to demonstrate the direct tubular effect(s) of ANP in rats, and to provide an evidence on a possible second messenger of ANP.1) Atrial natriuretic peptide (5-28AA; ANP) and atrial extract (ANS) stimulated rat renal gluconeogenesis in cortical tubule suspension in a dose dependent fashion only from substrates that enter gluconeogenesis via phosphoenolpyruvate carboxylase. The effects of ANP and ANS were significantly poteneiated by cAMP and cGMP, whereas methoxamine showed no effect. Extracellular calcium revealed a key role for ANP and ANS response to gluconeogenesis:a concentration of calcium higher than 1 mM was essential. Isolated cells from cortex which lost cell membrane polarity by warming but responded solely to cAMP and cGMP showed no effect by ANP nor ANS. These data suggest that ANP or ANS may act mainly from the basolateral site in the proximal tubule cell and promote gluconeogenesis through cAMP and/or cGMP system.2) Kidneys from male SD rats were treated with collagenase, and various parts of the nephron were microdissected. After incubation of individual nephron segments in Dulbecco minimal essential medium for 60 min at 37゜C, PGE_2 synthesized was quantified using RIA. PGE_2 producing activities were highly distributed in the medullary (MCT) and cortical collecting tubule (CCT). ANP (1-28AA) at 10^<-9> to 10^<-6>M increased PGE_2 production specifically in CCT, but not in MCT, indicating that ANP has a tubular effect in CCT on inhibiting NaCl reabsorption.3) ANP increased cGMP contents in the glomerulus, CCT and MDT. Exogeneous cGMP (10^<-3>M) increased PGE_2 only in CCT up to the similar level by excess ANP, suggesting that cGMP could be a second messenger of ANP.

虽然心房提取物和新合成的心房利钠肽（ANP）显示出强烈的利钠作用，但其在肾内的作用位点尚未明确。因此，本研究旨在证明ANP对大鼠肾小管的直接作用，并为ANP可能的第二信使提供证据。1)心房利钠肽（5-28AA； ANP）和心房提取物（ANS）仅通过通过磷酸烯醇丙酮酸羧化酶进入糖异生的底物，以剂量依赖的方式刺激皮质小管悬液中的大鼠肾糖异生。cAMP和cGMP可显著增强ANP和ANS的作用，而甲氧沙明对ANP和ANS的作用无明显影响。细胞外钙揭示了ANP和ANS对糖异生反应的关键作用：高于1mm的钙浓度是必需的。仅对cAMP和cGMP有反应的离体皮质细胞因温度升高而失去细胞膜极性，而ANP和ANS对其没有影响。这些数据表明，ANP或ANS可能主要从近端小管细胞的基底外侧起作用，并通过cAMP和/或cGMP系统促进糖异生。2)用胶原酶处理雄性SD大鼠肾脏，显微解剖肾单位各部位。单个肾元片段在Dulbecco最小基本培养基中37℃孵育60 min后，采用RIA定量合成PGE_2。PGE_2的生成活性主要分布在髓质（MCT）和皮质集小管（CCT）。10^<-9> ~ 10^<-6>M的ANP （1-28AA）在CCT中特异地增加了PGE_2的生成，而在MCT中没有，表明ANP在CCT中具有管状抑制NaCl重吸收的作用。3) ANP增加肾小球cGMP含量，增加CCT和MDT含量。外源性cGMP （10^<-3>M）仅在CCT中通过过量ANP使PGE_2升高至相似水平，提示cGMP可能是ANP的第二信使。