114471-18-0 Usage
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. BNP
solution in water at >10-4M is stable for more than a year
at -20°C.
Gene, mRNA, and precursor
The BNP (NPPB) and atrial natriuretic peptide (ANP)
genes (NPPA) are thought to be generated by the tandem
duplication of the CNP3 gene (NPPC). The human NPPA
and NPPB are located on chromosome 1 (1p36.22). The
mouse BNP and ANP genes (Nppb and Nppa) are on chromosome 4. NPPB is composed of three exons. Human
BNP mRNA is 708 bp (405 bp coding sequence). One of
the characteristics of BNP mRNA is a repetitive AUUUA
motif in the 30
-untranslated region. The motif is considered to destabilize mRNA, and does not exist in ANP
mRNA, suggesting that NPPB is regulated differently
from NPPA. Human proBNP is O-glycosylated posttranslationally. O-Glycosylated proBNP is further processed by specific convertases (probably furin
and corin) to give rise to the bioactive, mature form of
BNP and inactive N-terminal (NT)-proBNP. It is suggested that the cleavage of proBNP is regulated by
O-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 via
a regulatory pathway (except BNP in the atrium, where
BNP is stored and secreted with ANP). BNP production
is 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; thyroid
hormone-responsive elements; and the nuclear factor of
the activated T-cell (NFAT) binding site. Putative transcription factors are GATA4, YY1, and KLF13.5 BNP
expression in cardiomyocytes is enhanced by mechanical
stretch, 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 a
guanylyl cyclase domain that produces cGMP. The order
of potency for cGMP production via NPR-A is
ANP≥BNP≥CNP in humans. Another receptor is
the C-type NP receptor (NPR-C). The NPR-C lacks a
cytoplasmic guanylyl cyclase domain, and acts as a
clearance receptor. Affinities of NPR-C to NPs are
ANP>CNP>BNP in humans. The longer half-life of
plasma BNP is attributable mainly to the lower susceptibility to NPR-C. In mammals, NPR-A is highly
expressed in the adrenal, brain, kidney, adipose, aortic,
and lung tissues, whereas NPR-C is found ubiquitously
in most tissues. For more details on NPR-A and NPR-C,
the signaling transduction pathway, and the agonists/
antagonists, Atrial natriuretic
peptide
Biological functions
The biological actions of BNP are overlapped with those
of ANP because they share the same functional receptor,
NPR-A .
Briefly, BNP induces natriuresis and diuresis by increasing
the glomerular filtration rate and decreasing water and
sodium reabsorption by the kidney. In addition, BNP
decreases aldosterone secretion from the adrenal and vasopressin secretion from the posterior pituitary, which also
accelerates natriuresis and diuresis. BNP also decreases
systemic vascular resistance by its direct vasorelaxant
action. Thus, the net effect of BNP is to decrease blood volume (preload) and systemic blood pressure (afterload),
thereby protecting cardiac function. In eels, again similarly
to ANP actions, BNP decreases water intake, plasma
sodium concentration, and aortic pressure, but the effect
is weaker than that of ANP and VNP in the case of eels that
have VNP.
Clinical implications
The elevation of plasma BNP concentration is seen in
patients with congestive heart failure (CHF), myocardial
infarction, hypertension, left ventricular hypertrophy,
and chronic renal failure. Although the plasma ANP
level is also elevated by such pathological conditions,
the increment of the BNP level is quicker and greater than
that of ANP. In CHF, for instance, the plasma BNP and
ANP concentrations increase 200–300-fold and
10–30-fold, respectively, compared with those in normal
humans. The greater increase in BNP level is probably
due to its longer half-life in plasma. Thus, the plasma
BNP level is used as a reliable biomarker of both ischemic
and CHF. NT-proBNP cleaved with the BNP precursor
has a longer half-life (about 120min), and thus is used as
a more reliable marker for the diagnosis of heart failure. Recent studies showed that a high level of O-glycosylated
proBNP circulates in patients with severe heart failure.
Description
B-type natriuretic peptide is the only cardiac natriuretic peptide common to all
vertebrate species thus far examined. The plasma BNP level
is used as a robust and reliable biomarker for the diagnosis
and prognosis of heart failure. BNP was isolated in 1988 from porcine brain extracts
and was thus named the brain natriuretic peptide. Soon
thereafter, BNP was found to be expressed abundantly in
the cardiac ventricle and scarcely in the brains of humans
and 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 Heart
Association (NYHA) functional classification is correlated positively with the elevation of plasma BNP and
NT-proBNP levels. Therefore, these peptides are used
for the diagnosis and management of patients with
CHF. The use of a recombinant BNP, nesiritide, for treatment has been approved by the US Food and Drug
Administration. It has beneficial effects in patients with
acute, decompensated heart failure; however, it is
reported to increase the risk of renal dysfunction and
mortality. Further evaluation is required for the clinical
use 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), BNP
has an intramolecular ring consisting of 17 aa residues
and N- and C-terminal extensions of varying length.
All vertebrate species (tetrapods and fish) except for
chondrichthyes and cyclostomes possess BNP.2 Thus,
the BNP gene (nppb) is considered to have occurred
before the divergence of ray-finned fish and lobefinned fish. The sequence identity of mature BNP is quite variable
in mammals (<50% identity between human and mouse
BNP), whereas the identity is relatively high among
nonmammalian vertebrates.
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.
Check Digit Verification of cas no
The CAS Registry Mumber 114471-18-0 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,1,4,4,7 and 1 respectively; the second part has 2 digits, 1 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 114471-18:
(8*1)+(7*1)+(6*4)+(5*4)+(4*7)+(3*1)+(2*1)+(1*8)=100
100 % 10 = 0
So 114471-18-0 is a valid CAS Registry Number.
InChI:InChI=1/C143H244N50O42S4/c1-13-76(10)112-137(232)189-99(68-199)131(226)188-98(67-198)130(225)187-97(66-197)129(224)186-96(65-196)117(212)166-59-105(202)169-90(52-72(2)3)114(209)163-61-107(204)171-100(132(227)177-83(32-19-22-44-146)124(219)190-111(75(8)9)136(231)184-91(53-73(4)5)127(222)175-84(34-24-46-159-141(151)152)121(216)174-85(35-25-47-160-142(153)154)122(217)185-94(139(234)235)55-78-57-157-71-167-78)69-238-239-70-101(172-108(205)62-165-116(211)95(64-195)170-106(203)60-162-113(208)87(38-39-103(148)200)181-135(230)110(74(6)7)191-126(221)89(41-51-237-12)179-120(215)82(31-18-21-43-145)180-134(229)102-37-27-49-193(102)138(233)79(147)63-194)133(228)182-92(54-77-28-15-14-16-29-77)115(210)164-58-104(201)168-80(33-23-45-158-140(149)150)118(213)173-81(30-17-20-42-144)119(214)178-88(40-50-236-11)123(218)183-93(56-109(206)207)128(223)176-86(125(220)192-112)36-26-48-161-143(155)156/h14-16,28-29,57,71-76,79-102,110-112,194-199H,13,17-27,30-56,58-70,144-147H2,1-12H3,(H2,148,200)(H,157,167)(H,162,208)(H,163,209)(H,164,
