Cardiac hormones and neuroendocrine function.
Cardiac hormones and neuroendocrine function.
复制标题
心脏激素和神经内分泌功能。
DOI：
10.1007/978-1-4684-5799-5_11
复制
发表时间：
1990
影响因子：
--
通讯作者：
Samson,WK
中科院分区：
文献类型：
--
作者：
Samson,WK
有大量证据表明，心脏除了作为肌肉泵的功能外，还是一种内分泌组织，可分泌具有多种生物学作用的强效肽家族（1，2）。首先由Flynn及其同事（3）描述，心房利钠肽（ANP）在心房和心室肌细胞中通过常规蛋白质合成产生，但非常规翻译后加工（4-7）。这些肽分泌的主要刺激是由静脉回流增加引起的心房牵张（8，9），尽管已经描述了激素（10-12）和神经药物（13，14）的相互作用。ANP的主要分泌形式是具有由内部二硫键形成的17元环结构的28个氨基酸的肽，其对于该激素的生物活性的表达是必需的（15）。在大鼠中，ANP最初合成为较大分子量的前体，即152个氨基酸的prepro-ANP，并作为126个氨基酸的激素原proANP储存在分泌颗粒中（4-7）。翻译后加工的最后一步，即在分泌时发生的98和99位之间Arg-Ser键的裂解（6，7），产生成熟的28个氨基酸的激素和一小部分N-和C-末端缩短的片段。这些肽在循环中明显不与血浆蛋白结合，半衰期极短，约为30秒（16）。ANP主要在肾脏中从血浆中去除（17，18），尽管通过清除受体从血浆中隔离（19）也起重要作用。至少有两种类型的ANP被鉴定，一种最近被克隆和结构测序（20）被称为B受体。该受体被认为是生物受体，ANP通过该受体通过颗粒鸟苷酸环化酶的活化发挥其主要作用（21）。
There is abundant evidence that the heart, in addition to its function as a muscular pump, is an endocrine tissue which secretes a potent family of peptides with diverse biologic actions (1,2). First described by Flynn and colleagues (3), the atrial natriuretic peptides (ANPs) are produced by conventional protein synthesis, yet unconventional post-translational processing (4–7), in atrial and ventricular myocytes. The primary stimulus for secretion of these peptides is atrial stretch (8,9), induced by increased venous return, although interactive effects of hormones (10–12) and neural agents (13,14) have been described. The major secreted form of ANP is the 28 amino acid peptide possessing a 17 membered ring structure formed by an internal disulfide bond which appears necessary for the expression of this hormone’s bioactivity (15). In the rat ANP is initially synthesized as a larger molecular weight precursor, the 152 amino acid prepro-ANP, and is stored in secretory granules as the 126 amino acid prohormone, proANP (4–7). The final step in postranslational processing, cleavage of the Arg-Ser bond between positions 98 and 99, which occurs at the time of secretion (6,7), generates the mature 28 amino acid hormone and a small percentage of N- and C- terminally shortened fragments. The peptides circulate apparently unbound to plasma proteins and display an extremely short half-life, approximately 30 seconds (16). ANP is removed from plasma primarily in the kidney (17,18), although sequestration from plasma by clearance receptors (19) plays an important role as well. At least two classes of ANP been identified, one recently cloned and structurally sequenced (20) is called the B receptor. This receptor is thought to be the biologic receptor through which ANP exerts its major actions, via activation of particulate guanylate cyclase (21).