Physiological role of silent receptors of atrial natriuretic factor

A ring-deleted analog of atrial natriuretic factor--des[Gln18, Ser19, Gly20, Leu21, Gly22] ANF4-23-NH2 (C-ANF4-23)--binds with high affinity to approximately 99% of ANF receptors in the isolated perfused rat kidney. In this preparation, C-ANF4-23 is devoid of detectable renal effects and does not antagonize any of the known renal hemodynamic and natriuretic actions of biologically active ANF1-28. In contrast, both C-ANF4-23 and ANF1-28 increase sodium excretion and decrease blood pressure in intact anesthetized rats. This apparent contradiction is resolved by the finding that the ring-deleted analog markedly increases plasma levels of endogenous immunoreactive ANF in the rat. The results show that the majority of the renal receptors of ANF are biologically silent. This new class of receptors may serve as specific peripheral storage-clearance binding sites, acting as a hormonal buffer system to modulate plasma levels of ANF.     

Nucleotide sequences of the human and mouse atrial natriuretic factor genes

Mouse and human atrial natriuretic factor (ANF) genes have been cloned and their nucleotide sequences determined. Each ANF gene consists of three coding blocks separated by two intervening sequences. The 5' flanking sequences and those encoding proANF are highly conserved between the two species, while the intervening sequences and 3' untranslated regions are not. The conserved sequences 5' of the gene may play an important role in the regulation of ANF gene expression.     

Biosynthesis and secretion of proatrial natriuretic factor by cultured rat cardiocytes

Rat atrial natriuretic factor (ANF) is translated as a 152-amino acid precursor preproANF. PreproANF is converted to the 126-amino acid proANF, the storage form of ANF in the atria. ANF isolated from the blood is approximately 25 amino acids long. It is demonstrated here that rat cardiocytes in culture store and secrete proANF. Incubation of proANF with serum produced a smaller ANF peptide. PreproANF seems to be processed to proANF in the atria, and proANF appears to be released into the blood, where it is converted by a protease to a smaller peptide.     

Coexistence of guanylate cyclase and atrial natriuretic factor receptor in a 180-kD protein

Atrial natriuretic factor (ANF) is a peptide hormone that is released from atria and regulates a number of physiological processes, including steroidogenesis in adrenal cortex and testes. The parallel stimulation of membrane guanylate cyclase and corticosterone production in isolated fasciculata cells of rat adrenal cortex has supported the hypothesis of a mediatory role for cyclic guanosine monophosphate (cyclic GMP) in signal transduction. A novel particulate guanylate cyclase tightly coupled with ANF receptor was purified approximately 273,000-fold by two-step affinity chromatography. The enzyme had a molecular size of 180 kilodaltons and was acidic in nature with a pI of 4.7. Its specific activity was 1800 nanomoles of cyclic GMP formed per minute per milligram of protein. The purified enzyme bound ANF with a specific binding activity of 4.01 nanomoles per milligram of protein, a value that is close to the theoretical binding activity of 5.55 nanomoles per milligram of protein for 1 mole of the ligand binding 1 mole of the receptor protein. These results indicate that the guanylate cyclase-coupled ANF receptor exists in a 180-kilodalton protein of rat adrenocortical carcinoma and represent a step toward the elucidation of the basic mechanism of cyclic GMP-mediated transmembrane signal transduction in response to a hormone.     

The structure of rat preproatrial natriuretic factor as defined by a complementary DNA clone

The structure of rat preproatrial natriuretic factor ( preproANF ) was determined by nucleotide sequence analysis of an ANF complementary DNA clone. PreproANF is composed of a hydrophobic leader segment (20 amino acids), a precursor containing one glycosylation site (106 amino acids), and ANF (24 amino acids). Atrial natriuretic factor is located at the carboxyl terminus of the precursor molecule. The human, mouse, and rat genomes each contain a single ANF gene which is highly conserved.     

Inhibition of aldosterone production by an atrial extract

Crude extracts of rat atria reduced the basal amount of aldosterone released from rat zona glomerulosa cells and partially inhibited aldosterone stimulation by adrenocorticotropic hormone and angiotensin II. The destruction of this activity by trypsin suggests that the active factor is a peptide, possibly atrial natriuretic factor. These data suggest that atrial natriuretic factor affects sodium excretion by the kidneys both directly and through the inhibition of aldosterone production.     

Inhibition of vasopressin action by atrial natriuretic factor

Atrial natriuretic factor results in diuresis in animals and humans, perhaps because atrial natriuretic factor increases renal blood flow. The possibility that this diuresis is due to direct inhibition of renal tubular epithelial water transport was examined in rabbit collecting tubules perfused in vitro. Atriopeptin III inhibition of the hydraulic conductivity response to the hormone arginine vasopressin but not to either 3'5'-cyclic adenosine monophosphate or forskolin was found. These results suggest that atriopeptin III acts proximal to cyclic adenosine monophosphate formation to directly affect vasopressin-stimulated water transport in the mammalian nephron. They also suggest a potential role for inhibition by atrial natriuretic factor of the renal response to arginine vasopressin as a contributor to a diuretic state.     

Atrial natriuretic peptide elevation in congestive heart failure in the human

A sensitive radioimmunoassay for atrial natriuretic peptide was used to examine the relation between circulating atrial natriuretic peptide and cardiac filling pressure in normal human subjects, in patients with cardiovascular disease and normal cardiac filling pressure, and in patients with cardiovascular disease and elevated cardiac filling pressure with and without congestive heart failure. The present studies establish a normal range for atrial natriuretic peptide in normal human subjects. These studies also establish that elevated cardiac filling pressure is associated with increased circulating concentrations of atrial natriuretic peptide and that congestive heart failure is not characterized by a deficiency in atrial natriuretic peptide, but with its elevation.     

Cardiac atria of BIO 14.6 hamsters are deficient in natriuretic factor

The hearts of 220-day-old hamsters of the BIO 14.6 strain are deficient in atrial natriuretic factor; saline extracts of atria produce one-third the natriuretic and diuretic effects of extracts of atria from age-matched normal hamsters. BIO 14.6 hamsters are known to develop congestive heart failure with edema when they are about 200 days old, and the venous congestion and edema are preventable by parabiosis with normal hamsters. The humoral mediator, the deficiency of which causes venous congestion and edema in BIO 14.6 hamsters, may be atrial natriuretic factor.     

Atrial natriuretic peptide inhibits a cation channel in renal inner medullary collecting duct cells

The patch-clamp technique was used to examine the effects of atrial natriuretic peptide (ANP) and its second messenger guanosine 3',5'-monophosphate (cGMP) on an amiloride-sensitive cation channel in the apical membrane of renal inner medullary collecting duct cells. Both ANP (10(-11) M) and dibutyryl guanosine 3',5'-monophosphate (10(-4) M) inhibited the channel in cell-attached patches, and cGMP (10(-5) M) inhibited the channel in inside-out patches. The inner medullary collecting duct is the first tissue in which ANP, via its second messenger cGMP, has been shown to regulate single ion channels. The results suggest that the natriuretic action of ANP is related in part to cGMP-mediated inhibition of electrogenic Na+ absorption by the inner medullary collecting duct.     

Corrections and clarifications

In figure ID (p. 680) of the report "Genetic decreases in atrial natriuretic peptide and salt-sensitive hypertension" by Simon W. M. John et al. (3 Feb., p. 679), the size bars to the right and left of the Southern blot were not correctly aligned in relation to the dark bands.     

桂西北喀斯特山区非共生固氮速率随退耕后生态演替变化特征

非共生固氮是自然生态系统外源氮输入的重要途径,对生态系统结构、过程和功能均具有重要影响。然而,目前对非共生固氮速率随生态演替变化特征及其主控因素的认识非常欠缺。本研究采用乙炔还原法分别在生长季和非生长季测定了桂西北喀斯特山区不同演替阶段生态系统,即草丛、灌丛和次生林中不同组分(土壤、凋落物和苔藓)的非共生固氮速率。结果表明,不同生态系统组分非共生固氮速率随生态演替变化趋势不一。总体来看,土壤和凋落物的非共生固氮速率表现为随生态演替先降低后升高的趋势,而苔藓的非共生固氮速率在演替早期和中期无显著(p 0.05)变化,后期显著(p 0.05)升高。非共生固氮年通量在草丛阶段为(1.21±0.06) kg N/(hm~2·a),显著高于灌丛((0.23±0.03) kg N/(hm~2·a))和次生林((0.65±0.04) kg N/(hm~2·a))。多元线性回归分析结果表明,生态系统各组分含水率、有机碳、全氮和C∶N比的变化是控制非共生固氮速率随生态演替变化的主要因素。研究结果有助于深入认识喀斯特生态系统氮循环特征,并为生态恢复过程中氮累积提供了一种机理解释。     

Coronary vasoconstrictor effects of atriopeptin II

Atrial natriuretic peptides lower arterial pressure, cardiac filling pressure, and cardiac output. In isolated, Langendorff-perfused guinea pig hearts, atriopeptin II, the 23-amino acid atrial natriuretic peptide, is also a potent coronary vasoconstrictor. The median effective dose for atriopeptin II in guinea pig hearts is 26 nanomoles, the threshold constrictor dose is 5 nanomoles, and flow nearly ceases at a dose of 100 nanomoles in perfused hearts at constant pressure. Similar concentrations of atriopeptin II also cause coronary vasoconstriction in rat and dog heart preparations. The disulfide bridge is necessary for vasoconstrictor activity; reduction of this bridge abolishes the activity, as it does the other biological activities of atrial natriuretic peptides.     

大鼠急性肾功能衰竭时血浆心钠素与血管紧张素系统的关系

用顺铂（ＣＰ）诱发的大鼠急性肾功能衰竭（ＡＲＦ）动物实验模型，观察在急性肾功能衰竭发展的不同阶段血浆心钠素与肾素、血管紧张素系统之间的关系。发现在ＣＰ处置后２４、４８和７２ｈ，血清肌酐水平分别为正常对照组的１．５、２．５和４倍，同时血浆心钠素水平升高到１．８、２．７和３．６倍。而血浆肾素、血管紧张素系统的活性则相反，血浆肾素在２４ｈ末为正常对照组的２．５倍降低到４８ｈ的１．６倍，并于ＣＰ处置后７２ｈ恢复到正常对照组水平。血管紧张素在２４ｈ末为正常对照组４倍，在４８ｈ末下降４１％，７２ｈ末下降５８％，这表明在急性肾功能衰竭发展过程中，体内分泌的心钠素可能是通过拮抗肾素、血管紧张素系统从而起到肾功能保护的作用。     

人类3个多肽基因的人工合成和对人工基因合成意义的探讨

本文报道了胰岛素A,B链基因,人表皮生长因子基因和人α心钠素基因的人工合成。人工合成是在DNA合成仪上完成的,先合成上述基因的平均为60个核苷酸的各寡核苷酸片段,经过对各片段的纯化、磷酸化和连接,得到上述多肽基因。并进行了电泳检测。人工基因合成的重要意义在于可以正确地、高效地合成基因工程所需的基因,是获得在原核生物中表达的多肽基因的主要途径,并可将重组DNA和表达所需的碱基顺序同时组合在合成的基因中。人工基因合成有广泛的应用前途和价值。     

The generation of insulin-like growth factor-1--sensitive cells by growth hormone action

Insulin-like growth factor-1 (IGF-1), a mitogenic polypeptide, is usually considered the sole effector by means of which growth hormone increases tissue mass. However, growth hormone, but not IGF-1, directly promotes the differentiation of cultured preadipocytes to adipocytes. Adipocytes newly differentiated from precursor cells in response to growth hormone were shown to be much more sensitive to the mitogenic effect of IGF-1 than the precursor cells. The result of IGF-1 action is therefore a selective multiplication of young differentiated cells (cloned expansion). This supports the concept of a dual effector system in which the preferred target cells of IGF-1 action are created by the direct action of growth hormone.     

新生儿缺氧缺血性脑病心房利钠多肽血浆水平的检测及其与低钠血症的关系

目的 :观察血浆心房利钠多肽 (ANP)在新生儿缺氧缺血性脑病 (HIE)中的变化及与低钠血症的关系。方法 :采用放射免疫法分别检测 49例 HIE足月儿在治疗前后及 2 0例正常足月儿血浆 ANP水平 ,同时测定血清钠浓度 ,并将 ANP与血钠作相关性分析。结果 :HIE组血浆 ANP水平明显高于对照组 (P<0 .0 1 ) ,HIE程度愈重 ,ANP水平愈高 ,HIE组治疗后血浆 ANP水平明显低于治疗前水平 (P<0 .0 0 1 ) ;血浆 ANP与血清钠浓度呈显著负相关 (r=- 0 .6632 ,P<0 .0 0 1 )。结论 :血浆 ANP可反映 HIE患儿脑损伤的程度和预后 ,并可影响新生儿 HIE水盐代谢 ,引起失钠性低钠血症。     

Release of multiple hormones by a direct action of interleukin-1 on pituitary cells

Exposure to bacterial endotoxins has long been known to stimulate the release of anterior pituitary hormones; administration of endotoxin was at one time a common clinical test of anterior pituitary function. Endotoxin is a potent stimulus for production of the endogenous pyrogenic protein, interleukin-1 (IL-1), by macrophages and monocytes. The possibility that IL-1 has a direct effect on the secretion of hormones by rat pituitary cells in a monolayer culture was investigated. Recombinant human IL-1 beta stimulated the secretion of adrenocorticotropic hormone, luteinizing hormone, growth hormone, and thyroid-stimulating hormone. Increased hormone secretion into culture supernatants was found with IL-1 concentrations ranging from 10(-9) M to 10(-12) M. Prolactin secretion by the monolayers was inhibited by similar doses. These concentrations of IL-1 are within the range reported for IL-1 in serum, suggesting that IL-1 generated peripherally by mononuclear immune cells may act directly on anterior pituitary cells to modulate hormone secretion in vivo. Incubation of IL-1 solutions with antibody to IL-1 neutralized these actions. These pituitary effects of IL-1 suggest that this monokine may be an important regulator of the metabolic adaptations to infectious stressors.     

Release of luteinizing hormone in male mice during exposure to females: habituation of the response

Male mice release luteinizing hormone when exposed for a short time to a female. In this experiment, multiple blood samples were withdrawn by atrial cannulas from tethered males during either continuous or intermittent exposure to nonreceptive females. After an immediate, transient release of luteinizing hormone, continuous exposure to the same female was accompanied by only random, spontaneous elevations in plasma levels of this hormone. Successive presentations of the same female at 2-hour intervals elicited gradually diminishing luteinizing hormone responses. Exposing such unresponsive males to novel, diestrous females, however, dramatically stimulated their release of the hormone. These results demonstrate habituation of a socially induced, neuroendocrine response involving reproductive hormones.     

脑钠肽生物学特性及其在心血管病中的应用

脑钠肽（BNP）主要是由心脏分泌和存储的一种神经内分泌激素,为32个氨基酸组成的多肽片段,具有抑制肾素-血管紧张素-醛固酮系统（RAAS）和交感神经系统（SNS）等功能,BNP水平的检测已逐渐被应用于临床,在诊断心力衰竭、心源性哮喘与支气管哮喘的鉴别、评估急性心肌梗死范围等方面具有较大的应用价值,现已成为广大学者关注的焦点.