Inagami T
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232.
J Clin Pharmacol. 1994 May;34(5):424-6. doi: 10.1002/j.1552-4604.1994.tb04982.x.
Atrial natriuretic factor, originally isolated from the atrium of the heart, has been found to consist of three major groups: atrial natriuretic peptide (ANP), B-form natriuretic peptide (BNP), and C-form natriuretic peptide (CNP). In addition, ANP exists in its precursor form, pro-ANP, an active ANP with a longer peptide chain (urodilatin) and an antiparallel dimer of active ANP. Sites and production of these diverse forms of the peptides are also diverse, depending on pathologic states. Three major subtypes of ANP receptors exist; these include a clearance receptor and two types of a transmembrane receptor with guanylyl cyclase structures in their intracellular domain. The latter exists at least in two forms, one of which is found mainly in the brain. All the actions of ANP mediated by the transmembrane form of ANP receptors are mediated by cGMP generated by the guanylyl cyclase in the cytosolic domain of the receptor. Among the numerous effects of ANP, its major effects are stimulation of natriuresis and diuresis by the kidney through its hemodynamic and tubular effects. In addition, ANP causes vasodilatation and fluid volume reduction by direct actions on vascular smooth muscle cells, and inhibition of secretion of hormones, such as aldosterone, from adrenal cortex and norepinephrine from peripheral adrenergic neurons. Centrally mediated effects on the regulation of the fluid volume may also be important.
心房利钠因子最初是从心脏心房中分离出来的,现已发现它由三大类组成:心房利钠肽(ANP)、B型利钠肽(BNP)和C型利钠肽(CNP)。此外,ANP以其前体形式即前ANP存在,还有一种具有较长肽链的活性ANP(尿钠排泄肽)以及活性ANP的反平行二聚体。这些不同形式肽的产生部位也各不相同,这取决于病理状态。存在三种主要的ANP受体亚型;其中包括一种清除受体和两种在细胞内结构域具有鸟苷酸环化酶结构的跨膜受体。后者至少以两种形式存在,其中一种主要存在于大脑中。由ANP受体跨膜形式介导的ANP的所有作用都是由受体胞质结构域中的鸟苷酸环化酶产生的cGMP介导的。在ANP的众多作用中,其主要作用是通过其血流动力学和肾小管作用刺激肾脏的尿钠排泄和利尿。此外,ANP通过直接作用于血管平滑肌细胞导致血管舒张和血容量减少,并抑制肾上腺皮质分泌醛固酮以及外周肾上腺素能神经元分泌去甲肾上腺素等激素。中枢介导的对血容量调节的作用可能也很重要。