| Properties | The Mr of mature human BNP is 3466 and the pI is ca.10. Both pro- and mature BNP are freely soluble in water,acid, and 67% acetone, but insoluble in 99% acetone. BNPsolution in water at >10-4M is stable for more than a yearat -20°C. |
| Gene, mRNA, and precursor | The BNP (NPPB) and atrial natriuretic peptide (ANP)genes (NPPA) are thought to be generated by the tandemduplication of the CNP3 gene (NPPC). The human NPPAand NPPB are located on chromosome 1 (1p36.22). Themouse BNP and ANP genes (Nppb and Nppa) are on chromosome 4. NPPB is composed of three exons. HumanBNP mRNA is 708 bp (405 bp coding sequence). One ofthe characteristics of BNP mRNA is a repetitive AUUUAmotif in the 30-untranslated region. The motif is considered to destabilize mRNA, and does not exist in ANPmRNA, suggesting that NPPB is regulated differentlyfrom NPPA. Human proBNP is O-glycosylated posttranslationally. O-Glycosylated proBNP is further processed by specific convertases (probably furinand corin) to give rise to the bioactive, mature form ofBNP and inactive N-terminal (NT)-proBNP. It is suggested that the cleavage of proBNP is regulated byO-glycosylation at threonine-71. |
| Synthesis and release | BNP in the cardiac ventricle is secreted via a constitutive pathway as opposed to ANP secretion that occurs viaa regulatory pathway (except BNP in the atrium, whereBNP is stored and secreted with ANP). BNP productionis regulated transcriptionally and various regulatory elements are located in the 50-flanking region of NPPB,including GATA, M-CAT, and AP-1/CRE-like elements;NRSE; shear stress-responsive elements; thyroidhormone-responsive elements; and the nuclear factor ofthe activated T-cell (NFAT) binding site. Putative transcription factors are GATA4, YY1, and KLF13.5 BNPexpression in cardiomyocytes is enhanced by mechanicalstretch, TGF-β, and ET-1. |
| Receptors | BNP shares two receptors with ANP and VNP (cardiac NP found in ray-finned fish). The A-type NP receptor (NPR-A or GC-A) is a functional receptor, and has aguanylyl cyclase domain that produces cGMP. The orderof potency for cGMP production via NPR-A isANP≥BNP≥CNP in humans. Another receptor isthe C-type NP receptor (NPR-C). The NPR-C lacks acytoplasmic guanylyl cyclase domain, and acts as aclearance receptor. Affinities of NPR-C to NPs areANP>CNP>BNP in humans. The longer half-life ofplasma BNP is attributable mainly to the lower susceptibility to NPR-C. In mammals, NPR-A is highlyexpressed in the adrenal, brain, kidney, adipose, aortic,and lung tissues, whereas NPR-C is found ubiquitouslyin most tissues. For more details on NPR-A and NPR-C,the signaling transduction pathway, and the agonists/antagonists, Atrial natriureticpeptide |
| Biological functions | The biological actions of BNP are overlapped with thoseof ANP because they share the same functional receptor,NPR-A .Briefly, BNP induces natriuresis and diuresis by increasingthe glomerular filtration rate and decreasing water andsodium reabsorption by the kidney. In addition, BNPdecreases aldosterone secretion from the adrenal and vasopressin secretion from the posterior pituitary, which alsoaccelerates natriuresis and diuresis. BNP also decreasessystemic vascular resistance by its direct vasorelaxantaction. Thus, the net effect of BNP is to decrease blood volume (preload) and systemic blood pressure (afterload),thereby protecting cardiac function. In eels, again similarlyto ANP actions, BNP decreases water intake, plasmasodium concentration, and aortic pressure, but the effectis weaker than that of ANP and VNP in the case of eels thathave VNP. |
| Clinical implications | The elevation of plasma BNP concentration is seen inpatients with congestive heart failure (CHF), myocardialinfarction, hypertension, left ventricular hypertrophy,and chronic renal failure. Although the plasma ANPlevel is also elevated by such pathological conditions,the increment of the BNP level is quicker and greater thanthat of ANP. In CHF, for instance, the plasma BNP andANP concentrations increase 200–300-fold and10–30-fold, respectively, compared with those in normalhumans. The greater increase in BNP level is probablydue to its longer half-life in plasma. Thus, the plasmaBNP level is used as a reliable biomarker of both ischemicand CHF. NT-proBNP cleaved with the BNP precursorhas a longer half-life (about 120min), and thus is used asa more reliable marker for the diagnosis of heart failure. Recent studies showed that a high level of O-glycosylatedproBNP circulates in patients with severe heart failure. |
| Description | B-type natriuretic peptide is the only cardiac natriuretic peptide common to allvertebrate species thus far examined. The plasma BNP levelis used as a robust and reliable biomarker for the diagnosisand prognosis of heart failure. BNP was isolated in 1988 from porcine brain extractsand was thus named the brain natriuretic peptide. Soonthereafter, BNP was found to be expressed abundantly inthe cardiac ventricle and scarcely in the brains of humansand rats. Currently, BNP has been recognized as a principal cardiac hormone and referred to as the B-type natriuretic peptide. |
| Uses | hemostatic, antimicrobial |
| Clinical Use | The severity of CHF assessed by the New York HeartAssociation (NYHA) functional classification is correlated positively with the elevation of plasma BNP andNT-proBNP levels. Therefore, these peptides are usedfor the diagnosis and management of patients withCHF. The use of a recombinant BNP, nesiritide, for treatment has been approved by the US Food and DrugAdministration. It has beneficial effects in patients withacute, decompensated heart failure; however, it isreported to increase the risk of renal dysfunction andmortality. Further evaluation is required for the clinicaluse of nesiritide. |
| Structure and conformation | Human proBNP consists of 108 aa residues with bioactive mature BNP (47 aa residues) at the C-terminus. Like other natriuretic peptides (NPs), BNPhas an intramolecular ring consisting of 17 aa residuesand N- and C-terminal extensions of varying length.All vertebrate species (tetrapods and fish) except forchondrichthyes and cyclostomes possess BNP.2 Thus,the BNP gene (nppb) is considered to have occurredbefore the divergence of ray-finned fish and lobefinned fish. The sequence identity of mature BNP is quite variablein mammals (<50% identity between human and mouseBNP), whereas the identity is relatively high amongnonmammalian vertebrates. |
| Description | B-type Natriuretic Peptide Human is a polypeptide chain containing 32 amino acids and having a molecular mass of 3464 Dalton. The molecular formula is:C143H244N50O42S4. |
| Background | Natriuretic Peptide Precursor B acts as a cardiac hormone with a variety of biological actions including natriuresis, diuresis, vasorelaxation, and inhibition of renin and aldosterone secretion. It is thought to play a key role in cardiovascular homeostasis. Helps restore the body's salt and water balance. Improves heart function. |
| references | 1. Ziskoven D, Forssmann WG, Holthausen U, Menz G, Addicks K, Rippegater G: Calcium Calmodulinantagonists Influences the release of Cardiodilatin/ANP from Atrial Cardiocytes. Handbook Endocrinology of the Heart, edited by Kaufmann W, Wambach G, 01/1989; Springer Verlag Berlin Heidelberg New York;2. Maisel A, Krishnaswamy P, Nowak R, McCord J, Hollander J, Duc P, Omland T, Storrow A, Abraham W, Wu A, Clopton P, Steg P, Westheim A, Knudsen C, Perez A, Kazanegra R, Herrmann H, McCullough P (2002). "Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure". N Engl J Med 347 (3): 161–7.3. O'Connor CM, Starling RC, Hernandez AF, et al. Effect of nesiritide in patients with acute decompensated heart failure. TheNew Englandjournal of medicine 2011;365:32-43. |
