Meyer M, Schulz-Knappe P, Kuse E R, Hummel M, Hetzer R, Pichlmayr R, Forssmann W G
Niedersächsisches Institut für Peptid-Forschung (IPF), Medizinische Hochschule Hannover.
Anaesthesist. 1995 Feb;44(2):81-91. doi: 10.1007/s001010050135.
On the subject of natriuretic peptides there is a great deal of controversy, and intensive research efforts have been made studying their effects on electrolyte homeostasis. In the early 1980s, a peptide that caused diuresis, natriuresis, and had a relaxant effect on vascular smooth muscle was discovered independently by several groups. This was the breakthrough for the identification of natriuretic peptides, followed by the characterisation of the amino-acid sequences of several species. Synthesis of the peptide, cloning of the encoding gene, identification and characterisation of specific receptors, as well as the development of antibodies and radioimmuno-assays were rapidly accomplished. Research on the immunohistochemistry of cardiodilatin/atrial natriuretic peptide (CDD/ANP) and the regulation of CDD/ANP gene expression led to detection of the peptide in extra-atrial tissues. Later on, two new peptides were discovered brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP). These peptides share structural features with CDD/ANP with regard to their 17-amino-acid-exhibiting loop bridged by a disulfide bond. Another recently discovered peptide is urodilatin (URO), a renal-borne new member of A-type natriuretic peptide. URO was isolated from human urine and consists of the same sequence as CDD/ANP, containing the 17-amino-acid residue loop of the circulating hormone with 4 additional amino acids located at the NH2-terminus of the peptide. Regarding physiological actions, data strongly support a close association between URO and urinary sodium excretion. The application of URO in animals revealed a stronger diuresis and natriuresis with a lower influence on arterial blood pressure compared to CDD/ANP-99-126. These results were encouraging for the use of URO in clinical trials as a tool to prevent acute renal failure (ARF) in patients following heart transplantation and for treatment of incipient ARF in patients following liver transplantation. Summarising the results of these two studies, URO represents a new approach for not only prevention, but also for treatment of ARF following organ transplantation. This opens up new possibilities for the treatment of ARF of other origins in intensive care medicine.
关于利钠肽存在诸多争议，人们已投入大量研究精力来探究它们对电解质稳态的影响。20世纪80年代初，几个研究小组独立发现了一种能引起利尿、利钠且对血管平滑肌有舒张作用的肽。这是利钠肽鉴定方面的突破，随后对几种物种的氨基酸序列进行了表征。肽的合成、编码基因的克隆、特异性受体的鉴定和表征，以及抗体和放射免疫分析的开发都迅速完成。关于心钠素/心房利钠肽（CDD/ANP）的免疫组织化学研究以及CDD/ANP基因表达的调控导致在心房外组织中检测到该肽。后来，又发现了两种新的肽，即脑利钠肽（BNP）和C型利钠肽（CNP）。这些肽在具有由二硫键桥接的17个氨基酸的环方面与CDD/ANP具有共同的结构特征。另一种最近发现的肽是尿钠排泄肽（URO），它是A型利钠肽的肾脏来源新成员。URO是从人尿中分离出来的，其序列与CDD/ANP相同，包含循环激素的17个氨基酸残基环，在肽链氨基末端还有另外4个氨基酸。关于生理作用，数据有力地支持了URO与尿钠排泄之间的密切关联。与CDD/ANP - 99 - 126相比，URO在动物中的应用显示出更强的利尿和利钠作用，对动脉血压的影响较小。这些结果对于将URO用于临床试验作为预防心脏移植患者急性肾衰竭（ARF）以及治疗肝移植患者早期ARF的工具来说是令人鼓舞的。总结这两项研究的结果，URO不仅代表了预防器官移植后ARF的新方法，也代表了治疗ARF的新方法。这为重症监护医学中其他病因引起的ARF治疗开辟了新的可能性。
