Leitman D C, Murad F
Department of Physiology, Stanford University School of Medicine, California.
Endocrinol Metab Clin North Am. 1987 Mar;16(1):79-105.
Since the seminal discovery by deBold that atria contain factors that produce diuresis and natriuresis, the biologic effects attributed to ANF have expanded to the point where the name "atrial natriuretic factor" seems inappropriate. In addition to promoting diuresis and natriuresis, ANF has been shown to produce vascular smooth muscle relaxation and to inhibit the secretion of aldosterone from the adrenal cortex, renin from the juxtaglomerlular apparatus, vasopressin from the hypothalamus, and salt and water intake after central administration. ANF also promotes intestinal secretion and stimulates testosterone synthesis in Leydig cells. However, the cellular mechanisms whereby ANF elicits these diverse effects are poorly understood. ANF has been reported to inhibit adenylate cyclase in a number of tissues. However, the significance of ANF inhibition of adenylate cyclase is unknown. This effect cannot be associated with vascular relaxation since decreased cyclic AMP would be expected to promote contraction rather than relaxation. ANF inhibition of adenylate cyclase may mediate the inhibitory effects of ANF on hormone secretion from the anterior pituitary gland. The inhibition of adenylate cyclase could also explain the inhibitory effect of ANF on aldosterone synthesis, since agents that stimulate cyclic AMP increase aldosterone synthesis. However, ANF also inhibits the dibutyryl-cyclic AMP-induced stimulation of aldosterone secretion, suggesting that an inhibition of adenylate cyclase cannot account fully for the inhibitory effects of ANF on aldosterone synthesis. There is no evidence to support a role for cyclic AMP in the diuretic and natriuretic action of ANF. An inhibition of membrane phosphoinositide breakdown by ANF and the subsequent formation of IP3 and intracellular calcium release could explain the inhibitory effects of ANF on vascular contraction and steroid synthesis. However, there is very little evidence to suggest that ANF regulates phosphoinositide metabolism, while some recent studies suggest that ANF may regulate calcium fluxes in vascular tissue. Clearly, cyclic GMP has emerged as the most likely intracellular mediator of ANF effects. ANF increases cyclic GMP in a wide range of tissues by selectively activating particulate guanylate cyclase. However, it is not known which effects of ANF are mediated by cyclic GMP. The discovery that ANF increases cyclic GMP in vascular tissue clearly suggests that cyclic GMP mediates the vascular relaxation effect of ANF, since other classes of vasodilators also increase cyclic GMP. There is preliminary evidence that cyclic GMP may inhibit renin secretion and sodium transport in kidney cells.(ABSTRACT TRUNCATED AT 400 WORDS)
自从德博尔德做出开创性发现，即心房含有能产生利尿和利钠作用的因子以来，归因于心房钠尿肽（ANF）的生物学效应已扩展到这样的程度，以至于“心房钠尿因子”这个名称似乎并不合适。除了促进利尿和利钠作用外，ANF还被证明能使血管平滑肌舒张，并抑制肾上腺皮质醛固酮的分泌、肾小球旁器肾素的分泌、下丘脑抗利尿激素的分泌以及中枢给药后盐和水的摄入。ANF还能促进肠道分泌，并刺激睾丸间质细胞中睾酮的合成。然而，ANF引发这些不同效应的细胞机制却知之甚少。据报道，ANF在许多组织中能抑制腺苷酸环化酶。然而，ANF抑制腺苷酸环化酶的意义尚不清楚。这种效应与血管舒张无关，因为预期环磷酸腺苷（cAMP）减少会促进收缩而非舒张。ANF对腺苷酸环化酶的抑制作用可能介导了ANF对垂体前叶激素分泌的抑制作用。腺苷酸环化酶的抑制作用也可以解释ANF对醛固酮合成的抑制作用，因为刺激cAMP的物质会增加醛固酮的合成。然而，ANF也能抑制二丁酰 - cAMP诱导的醛固酮分泌，这表明腺苷酸环化酶的抑制不能完全解释ANF对醛固酮合成的抑制作用。没有证据支持cAMP在ANF的利尿和利钠作用中发挥作用。ANF对膜磷脂酰肌醇分解的抑制以及随后肌醇三磷酸（IP3）的形成和细胞内钙的释放可以解释ANF对血管收缩和类固醇合成的抑制作用。然而，几乎没有证据表明ANF调节磷脂酰肌醇代谢，而最近的一些研究表明ANF可能调节血管组织中的钙通量。显然，环磷酸鸟苷（cGMP）已成为ANF效应最可能的细胞内介质。ANF通过选择性激活颗粒型鸟苷酸环化酶，在广泛的组织中增加cGMP。然而，尚不清楚ANF的哪些效应是由cGMP介导的。ANF在血管组织中增加cGMP的发现清楚地表明，cGMP介导了ANF的血管舒张作用，因为其他类别的血管扩张剂也会增加cGMP。有初步证据表明，cGMP可能抑制肾素分泌和肾细胞中的钠转运。（摘要截选至400字）
