Atrial natriuretic peptide - wikipedia Atrial natriuretic peptide NPPA Available structures PDB Ortholog search : PDBe RCSB List of PDB id codes 1ANP, 1YK0, 3N57 Identifiers Aliases NPPA, ANF, ANP, ATFB6, ATRST2, CDD, CDD - ANF, CDP, PND, Atrial natriuretic peptide, natriuretic peptide A External IDs OMIM : 108780 MGI : 97367 HomoloGene : 4498 GeneCards : NPPA Gene location ( Human ) Chr. Chromosome 1 ( human ) Band 1p36. 22 Start 11,845,709 bp End 11,848,345 bp Gene location ( Mouse ) Chr. Chromosome 4 ( mouse ) Band 4 E2 4 78.66 cM Start 148,000,722 bp End 148,002,079 bp Gene ontology Molecular function neuropeptide receptor binding hormone activity peptide hormone receptor binding neuropeptide hormone activity protein binding receptor binding hormone receptor binding Cellular component cytoplasm mast cell granule Cell nucleus perinuclear region of cytoplasm extracellular region extracellular space extracellular matrix macromolecular complex Biological process response to muscle stretch positive regulation of cardiac muscle contraction response to hypoxia regulation of high voltage - gated calcium channel activity neuropeptide signaling pathway female pregnancy regulation of cardiac conduction negative regulation of collecting lymphatic vessel constriction positive regulation of potassium ion export across plasma membrane cellular protein metabolic process regulation of blood vessel size positive regulation of heart rate positive regulation of delayed rectifier potassium channel activity cGMP biosynthetic process regulation of blood pressure negative regulation of systemic arterial blood pressure regulation of calcium ion transmembrane transport via high voltage - gated calcium channel transcription initiation from RNA polymerase II promoter regulation of atrial cardiac muscle cell membrane repolarization response to insulin cell growth involved in cardiac muscle cell development negative regulation of cell growth cardiac muscle hypertrophy in response to stress cellular response to mechanical stimulus receptor guanylyl cyclase signaling pathway protein folding regulation of receptor activity positive regulation of histamine secretion by mast cell Sources : Amigo / QuickGO Orthologs Species Human Mouse Entrez 4878 230899 Ensembl ENSG00000175206 ENSMUSG00000041616 UniProt P01160 P05125 RefSeq ( mRNA ) NM_006172 NM_008725 RefSeq ( protein ) NP_006163 NP_032751 Location ( UCSC ) Chr 1 : 11.85 -- 11.85 Mb Chr 4 : 148 -- 148 Mb PubMed search Wikidata View / Edit Human View / Edit Mouse Atrial natriuretic peptide ( ANP ) is a peptide hormone which reduces an expanded extracellular fluid ( ECF ) volume by increasing renal sodium excretion. ANP is synthesized, and secreted by cardiac muscle cells in the walls of the atria in the heart. These cells contain volume receptors which respond to increased stretching of the atrial wall due to increased atrial blood volume. ANP is one of a family of nine natriuretic peptides : seven are atrial in origin. ANP acts on the kidney to increase sodium and water excretion ( natriuresis ) in the following ways : 1 ) it dilates the glomerular afferent and constricts efferent arterioles, and relaxes the mesangial cells. This increases pressure in the glomerular capillaries, increasing the glomerular filtration rate ( GFR ), resulting in an increased amount of sodium and water being filtered and excreted. 2 ) It increases blood flow through the vasa recta, which washes the solutes sodium chloride ( NaCl ) and urea out of the medullary interstitium -- the lower osmolarity here leads to less reabsorption of tubular fluid and increased excretion. 3 ) It decreases sodium reabsorption in the distal convoluted tubule and cortical collecting duct. 4 ) It inhibits renin secretion, thereby inhibiting the production of angiotensin and aldosterone. 5 ) It inhibits the renal sympathetic nervous system. ANP has the opposite effect of aldosterone on the kidney : aldosterone increases renal sodium retention and ANP increases renal sodium loss. Reduction of blood volume by ANP can result in secondary effects such as reduction of extracellular fluid ( ECF ) volume ( edema ), improved cardiac ejection fraction with resultant improved organ perfusion, decreased blood pressure, and increased serum potassium. These effects may be blunted or negated by various counter-regulatory mechanisms operating concurrently on each of these secondary effects. Brain natriuretic peptide ( BNP ) -- a misnomer ; it is secreted by cardiac muscle cells in the heart ventricles -- is similar to ANP in its effect. It acts via the same receptors as ANP does, but with 10-fold lower affinity than ANP. The biological half - life of BNP, however, is twice as long as that of ANP, and that of NT - proBNP is even longer, making these peptides better choices than ANP for diagnostic blood testing. Contents 1 Discovery 2 Structure 3 Production 4 Receptors 5 Physiological effects 5.1 Renal 5.2 Adrenal 5.3 Vascular 5.4 Cardiac 5.5 Adipose tissue 6 Degradation 7 Biomarker 8 Therapeutic use and drug development 9 Other natriuretic peptides 10 Pharmacological modulation 11 Synonyms 12 Outside reading 13 References 14 External links Discovery The discovery of ANP was reported in 1981, when rat atrial extracts were found to contain a substance that increased salt and urine output in the kidney. Later, the substance was purified from heart tissue by several groups and named atrial natriuretic factor ( ANF ) or ANP. Structure ANP is a 28 - amino acid peptide with a 17 - amino acid ring in the middle of the molecule. The ring is formed by a disulfide bond between two cysteine residues at positions 7 and 23. ANP is closely related to BNP ( brain natriuretic peptide ) and CNP ( C - type natriuretic peptide ), which all share a similar amino acid ring structure. ANP is one of a family of nine structurally similar natriuretic hormones : seven are atrial in origen. Production Human ANP is encoded by the NPPA gene on the short arm of chromosome 1, which has 3 exons and 2 introns. The gene is expressed primarily in atrial myocytes. Lower levels of NPPA expression are found in other tissues such as the brain, kidney, lung, uterus and placenta. In atrial myocytes, ANP is made as a precursor form, i.e. prepro - ANP, a polypeptide of 151 amino acids. After the signal peptide is removed in the endoplasmic reticulum, the 126 - amino - acid pro-ANP is stored in the intracellular granules. When the cells are stimulated, pro-ANP is released and converted to the 28 - amino - acid C - terminal mature ANP on the cell surface by the cardiac transmembrane serine protease corin. ANP is secreted in response to : Stretching of the atrial wall, via Atrial volume receptors Increased Sympathetic stimulation of β - adrenoceptors Increased sodium concentration ( hypernatremia ), though sodium concentration is not the direct stimulus for increased ANP secretion Endothelin, a potent vasoconstrictor Receptors Three types of atrial natriuretic peptide receptors have been identified on which natriuretic peptides act. They are all cell surface receptors and designated : guanylyl cyclase - A ( GC - A ) also known as natriuretic peptide receptor - A ( NPRA / ANP ) or NPR1 guanylyl cyclase - B ( GC - B ) also known as natriuretic peptide receptor - B ( NPRB / ANP ) or NPR2 natriuretic peptide clearance receptor ( NPRC / ANP ) or NPR3 NPR - A and NPR - B have a single membrane - spanning segment with an extracellular domain that binds the ligand. The intracellular domain maintains two consensus catalytic domains for guanylyl cyclase activity. Binding of a natriuretic peptide induces a conformational change in the receptor that causes receptor dimerization and activation. The binding of ANP to its receptor causes the conversion of GTP to cGMP and raises intracellular cGMP. As a consequence, cGMP activates a cGMP - dependent kinase ( PKG or cGK ) that phosphorylates proteins at specific serine and threonine residues. In the medullary collecting duct, the cGMP generated in response to ANP may act not only through PKG but also via direct modulation of ion channels. NPR - C functions mainly as a clearance receptor by binding and sequestering ANP from the circulation. All natriuretic peptides are bound by the NPR - C. Physiological effects Maintenance of the ECF volume ( space ), and its subcompartment the vascular space, is crucial for survival. These compartments are maintained within a narrow range, despite wide variations in dietary sodium intake. There are three volume regulating systems : two salt saving systems, the renin angiotensin aldosterone system ( RAAS ) and the renal sympathetic system ( RSS ) ; and the salt excreting natriuretic peptide ( NP ) hormone system. When the vascular space contracts, the RAAS and RSS are `` turned on '' ; when the atria expand, NP 's are `` turned on ''. Each system also suppresses its counteracting system ( s ). NP 's are made in cardiac, intestinal, renal, and adrenal tissue : ANP in one of a family of cardiac NP 's : others at BNP, CNP, and DNP. ANP binds to a specific set of receptors -- ANP receptors. Receptor - agonist binding causes the increase in renal sodium excretion, which results in a decreased ECF and blood volume. Secondary effects may be an improvement in cardiac ejection fraction and reduction of systemic blood pressure. Renal Dilates the afferent glomerular arteriole, constricts the efferent glomerular arteriole, and relaxes the mesangial cells. This increases pressure in the glomerular capillaries, thus increasing the glomerular filtration rate ( GFR ), resulting in greater filter load of sodium and water. Increases blood flow through the vasa recta, which will wash the solutes ( sodium chloride ( NaCl ), and urea ) out of the medullary interstitium. The lower osmolarity of the medullary interstitium leads to less reabsorption of tubular fluid and increased excretion. Decreases sodium reabsorption in the distal convoluted tubule ( interaction with NCC ) and cortical collecting duct of the nephron via guanosine 3 ', 5 ' - cyclic monophosphate ( cGMP ) dependent phosphorylation of ENaC. Its natriuretic effect is affected by dopamine and dopamine receptor D activity in vivo Inhibits renin secretion, thereby inhibiting the renin -- angiotensin -- aldosterone system. Adrenal Reduces aldosterone secretion by the zona glomerulosa of the adrenal cortex. Vascular Relaxes vascular smooth muscle in arterioles and venules by : Membrane Receptor - mediated elevation of vascular smooth muscle cGMP Inhibition of the effects of catecholamines Promotes uterine spiral artery remodeling, which is important for preventing pregnancy - induced hypertension. Cardiac Inhibits maladaptive cardiac hypertrophy Re-expression of NPRA rescues the phenotype. Adipose tissue Increases the release of free fatty acids from adipose tissue. Plasma concentrations of glycerol and nonesterified fatty acids are increased by i.v. infusion of ANP in humans. Activates adipocyte plasma membrane type A guanylyl cyclase receptors NPR - A Increases intracellular cGMP levels that induce the phosphorylation of a hormone - sensitive lipase and perilipin A via the activation of a cGMP - dependent protein kinase - I ( cGK - I ) Does not modulate cAMP production or PKA activity Degradation Modulation of the effects of ANP is achieved through gradual degradation of the peptide by the enzyme neutral endopeptidase ( NEP ). Recently, NEP inhibitors have been developed ; however they have not yet been licensed. They may be clinically useful in treating congestive heart disease. Biomarker Fragments derived from the ANP precursor, including the signal peptide, N - terminal pro-ANP and ANP, have been detected in human blood. ANP and related peptides are used as biomarkers for cardiovascular diseases such as stroke, coronary artery disease, myocardial infarction and heart failure. Large amounts of ANP secretion has been noted to cause electrolyte disturbances ( hyponatremia ) and polyuria. These indications can be a marker of a large atrial myxoma. Therapeutic use and drug development Recombinant human ANP has been approved in Japan to treat patients with heart failure. As of 2017 a truncated form of ANP called ularitide was under development in Phase III trials for heart failure. Other natriuretic peptides Brain natriuretic peptide ( BNP ) -- a misnomer ; it is secreted by ventricular myocytes -- is similar to ANP in its effect. It acts via atrial natriuretic peptide receptors but with 10-fold lower affinity than ANP. The biological half - life of BNP, however, is twice as long as that of ANP, and that of NT - proBNP is even longer, making these peptides better choices than ANP for diagnostic blood testing. In addition to the mammalian natriuretic peptides ( ANP, BNP, CNP ), other natriuretic peptides with similar structure and properties have been isolated elsewhere in the animal kingdom. A salmon natriuretic peptide known as salmon cardiac peptide has been described, and dendroaspis natriuretic peptide ( DNP ) has been found in the venom of the green mamba, as well as an NP in a species of African snake. Beside these four, five additional natriuretic peptides have been identified : long - acting natriuretic peptide ( LANP ), vessel dilator, kaliuretic peptide, urodilatin, and adrenomedullin. Pharmacological modulation Neutral endopeptidase ( NEP ) also known as neprilysin is the enzyme that metabolizes natriuretic peptides. Several inhibitors of NEP are currently being developed to treat disorders ranging from hypertension to heart failure. Most of them are dual inhibitors ( NEP and ACE ). In 2014, PARADIGM - HF study was published in NEJM. This study considered as a landmark study in treatment of heart failure. The study was double blinded ; compared LCZ696 versus enalapril in patients with heart failure. The study showed lower all cause mortality, cardiovascular mortality and hospitalization in LCZ696 arm. Omapatrilat ( dual inhibitor of NEP and angiotensin - converting enzyme ) developed by BMS did not receive FDA approval due to angioedema safety concerns. Other dual inhibitors of NEP with ACE / angiotensin receptor are ( in 2003 ) being developed by pharmaceutical companies. Synonyms ANP is also called atrial natriuretic factor ( ANF ), atrial natriuretic hormone ( ANH ), cardionatrine, cardiodilatin ( CDD ), and atriopeptin. Outside reading https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4855512/ Vesely Chapter 39, Antinatriureic peptides, in Seldin and Giebisch 's The Kidney, Fifth Edition. DOI : https://dx.doi.org/10.1016/B978-0-12-381462-3.00037-9. 2013 Elsevier Inc. 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Jump up ^ Saito Y ( Nov 2010 ). `` Roles of atrial natriuretic peptide and its therapeutic use ''. Journal of Cardiology. 56 ( 3 ) : 262 -- 70. doi : 10.1016 / j. jjcc. 2010.08. 001. PMID 20884176. Jump up ^ `` Ularitide ''. AdisInsight. Retrieved 6 August 2017. Jump up ^ Tervonen V, Arjamaa O, Kokkonen K, Ruskoaho H, Vuolteenaho O ( Sep 1998 ). `` A novel cardiac hormone related to A -, B - and C - type natriuretic peptides ''. Endocrinology. 139 ( 9 ) : 4021 -- 5. doi : 10.1210 / en. 139.9. 4021. PMID 9724061. Jump up ^ Schweitz H, Vigne P, Moinier D, Frelin C, Lazdunski M ( Jul 1992 ). `` A new member of the natriuretic peptide family is present in the venom of the green mamba ( Dendroaspis angusticeps ) ''. The Journal of Biological Chemistry. 267 ( 20 ) : 13928 -- 32. PMID 1352773. Jump up ^ Vesely Chapter 39, Antinatriureic peptides, in Seldin and Giebisch 's The Kidney, Fifth Edition. DOI : https://dx.doi.org/10.1016/B978-0-12-381462-3.00037-9. ( c ) 2013 Elsevier Inc. Jump up ^ McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR ( Sep 2014 ). `` Angiotensin - neprilysin inhibition versus enalapril in heart failure ''. The New England Journal of Medicine. 371 ( 11 ) : 993 -- 1004. doi : 10.1056 / NEJMoa1409077. PMID 25176015. Jump up ^ Venugopal J ( 2003 ). `` Pharmacological modulation of the natriuretic peptide system ''. Expert Opinion on Therapeutic Patents. 13 ( 9 ) : 1389 -- 1409. doi : 10.1517 / 13543776.13. 9.1389. External links Atrial Natriuretic Factor at the US National Library of Medicine Medical Subject Headings ( MeSH ) Human NPPA genome location and NPPA gene details page in the UCSC Genome Browser. Hormones Endocrine glands Hypothalamic - pituitary Hypothalamus GnRH TRH Dopamine CRH GHRH Somatostatin ( GHIH ) MCH Posterior pituitary Oxytocin Vasopressin Anterior pituitary FSH LH TSH Prolactin POMC CLIP ACTH MSH Endorphins Lipotropin GH Adrenal axis Adrenal cortex aldosterone cortisol cortisone DHEA DHEA - S androstenedione Adrenal medulla epinephrine norepinephrine Thyroid Thyroid hormone Calcitonin Thyroid axis Parathyroid PTH Gonadal axis Testis testosterone AMH inhibin Ovary estradiol progesterone activin and inhibin relaxin Placenta hCG HPL estrogen progesterone Pancreas glucagon insulin amylin somatostatin pancreatic polypeptide Pineal gland melatonin N, N - dimethyltryptamine 5 - methoxy - N, N - dimethyltryptamine Other Thymus Thymosins Thymosin α1 Beta thymosins Thymopoietin Thymulin Digestive system Stomach gastrin ghrelin Duodenum CCK Incretins GIP GLP - 1 secretin motilin VIP Ileum enteroglucagon peptide YY Liver / other Insulin - like growth factor IGF - 1 IGF - 2 Adipose tissue leptin adiponectin resistin Skeleton Osteocalcin Kidney renin EPO calcitriol prostaglandin Heart Natriuretic peptide ANP BNP Physiology of the kidneys and acid - base physiology Renal function Secretion clearance Pharmacokinetics Clearance of medications Urine flow rate Reabsorption Solvent drag sodium chloride urea glucose oligopeptides protein Renal function Glomerular filtration rate Creatinine clearance Renal clearance ratio Urea reduction ratio Kt / V Standardized Kt / V Measures of dialysis Hemodialysis product PAH clearance ( Effective renal plasma flow Extraction ratio ) Filtration Renal blood flow Ultrafiltration Countercurrent exchange Filtration fraction Hormones Antidiuretic hormone Aldosterone Atrial natriuretic peptide Renin Erythropoietin Calcitriol Prostaglandins Acid - base balance Fluid balance Darrow Yannet diagram Body water : Intracellular fluid / Cytosol Extracellular fluid ( Interstitial fluid Plasma Transcellular fluid ) Base excess Davenport diagram Anion gap Arterial blood gas Winters ' formula Buffering Bicarbonate buffer system Respiratory compensation Renal compensation Other Fractional sodium excretion BUN - to - creatinine ratio Tubuloglomerular feedback Natriuresis Urine Amyloidosis ( E85, 277.3 ) Common amyloid forming proteins AA ATTR Aβ2M AL Aβ / APP AIAPP ACal APro AANF ACys ABri Systemic amyloidosis AL amyloidosis AA amyloidosis Aβ2M / Haemodialysis - associated AGel / Finnish type AA / Familial Mediterranean fever ATTR / Transthyretin - related hereditary Organ - limited amyloidosis Heart AANF / Isolated atrial Brain Familial amyloid neuropathy ACys + ABri / Cerebral amyloid angiopathy Aβ / Alzheimer 's disease Kidney AApoA1 + AFib + ALys / Familial renal Skin Primary cutaneous amyloidosis Amyloid purpura Endocrine Thyroid ACal / Medullary thyroid cancer Pituitary APro / Prolactinoma Pancreas AIAPP / Insulinoma AIAPP / Diabetes mellitus type 2 Retrieved from `` https://en.wikipedia.org/w/index.php?title=Atrial_natriuretic_peptide&oldid=833936591 '' Categories : Genes on human chromosome 1 Peptide hormones Hormones of the heart Talk Contents About Wikipedia Català Čeština Deutsch ދިވެހިބަސް Español Français Gaeilge Galego 한국어 Հայերեն Italiano Македонски Nederlands 日本 語 Polski Português Română Русский Simple English Slovenščina Српски / srpski Srpskohrvatski / српскохрватски Suomi Svenska தமிழ் Türkçe Українська 中文 20 more Edit links This page was last edited on 3 April 2018, at 02 : 54. 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Question: what effect does anp have on blood pressure
Answer: decreased blood pressure