Intrarenal actions of atrial natriuretic peptides

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。本研究是设计的，因此，目的是演示ANP在大鼠中的直接管状效应（s），并提供关于ANP.1）初级自然肽（5- 28 AA; ANP）和初级提取物（ANS）中的刺激大鼠renalgluconeogenesis在一种依赖性时尚中的悬浮作用，仅从底物中通过磷酸烯醇吡酯羧化酶通过底物输入葡萄糖eogenesis。ANP和ANS的影响可能被cAMP和cGMP显著地影响，而methoxamine显示没有影响。Extracellular Calcium揭示了ANP和ANS对葡萄糖生成反应的关键作用：一个高于1毫米的Calcium的集中。来自Cortex的孤立细胞，其中丢失的细胞膜极化性被变暖但响应于cAMP和cGMP显示无效果的ANP nor ANS。这些数据建议ANP或ANS可能主要来自碱性位点的正管细胞和促糖生成，通过cAMP和/或cGMP系统. 2）来自男性SD大鼠的肾脏被用聚合酶处理，以及尼龙被微受污染的各种部分。Dulbecco最低限度的基本介质在37 ° C时培养个人肾上腺素片段后， PGE_2用RIA量化。PGE_2 producing activities were highly distributed in the medullary （MCT） and cortical collecting tubule （CCT）。ANP （1- 28 AA）在10^<-9>至10^<-6>M增加了PGE_2生产，但不在MCT中，指示ANP在CCT中对抑制NaCl吸附有管状效应. 3） ANP增加了cGMP含量在Glomerus、CCT和MDT中。Exogeneous cGMP （10^<-3>M）仅在CCT上增加到非常ANP的类似级别，建议cGMP可能是ANP的第二个信使。

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.