Atrial Natriuretic Peptide (ANP) (1-28), human, porcine Acetate is a bioactive peptide that plays a crucial role in the body's homeostatic mechanisms. Atrial Natriuretic Peptide (ANP) (1-28) inhibits angiotensin II)-induced endothelin-1 secretion in a dose-dependent manner[1]. Atrial Natriuretic Peptide (ANP) (1-28) is primarily secreted by atrial myocytes in response to increased atrial stretch, such as during volume overload. The 28-amino-acid sequence is highly conserved between human and porcine forms. The acetate modification may affect its solubility, stability, and biological activity to some extent[2]. Atrial Natriuretic Peptide (ANP) (1-28) binds to its specific receptors, mainly the guanylyl cyclase-linked natriuretic peptide receptor-A (NPR-A). The binding activates guanylyl cyclase, leading to an increase in intracellular cyclic guanosine monophosphate (cGMP) levels. Elevated cGMP then mediates a series of physiological effects. In the kidneys, Atrial Natriuretic Peptide (ANP) (1-28) promotes natriuresis (increased sodium excretion) and diuresis (increased urine output), which helps to reduce blood volume. The peptide achieves this by increasing the glomerular filtration rate, inhibiting sodium reabsorption in the renal tubules, and suppressing the renin-angiotensin-aldosterone system (RAAS)[3]. Atrial Natriuretic Peptide (ANP) (1-28) causes vasodilation of blood vessels, reducing peripheral vascular resistance and thus lowering blood pressure. Atrial Natriuretic Peptide (ANP) (1-28) also has anti-fibrotic and anti-hypertrophic effects on the heart, helping to prevent cardiac remodeling and maintain normal cardiac function[4].
In vitro, Atrial Natriuretic Peptide (ANP) (1-28) (10nmol/L) pretreated human embryonic kidney cells (HEK 293) for 30 minutes, significantly inhibited the aldosterone (500pmol/L)-induced nuclear translocation of the mineralocorticoid receptor (MR)[5]. Atrial Natriuretic Peptide (ANP) (1-28)(100nM) pretreated human pulmonary artery endothelial cells (HPAECs) for 20 minutes, significantly inhibited the increase in endothelial cell permeability induced by thrombin (0.5units/mL). Atrial Natriuretic Peptide (ANP) (1-28) inhibits the secretion of endothelin-1 in a dose-dependent manner, thereby suppressing the Rho signaling pathway, reducing myosin light chain (MLC) phosphorylation, and inhibiting stress fiber formation, thus alleviating cell contraction and increased permeability[6].
In vivo, Atrial Natriuretic Peptide (ANP) (1-28)(2µg in 400µL PBS per mouse) was intraperitoneally injected into mice with DSS-induced colitis. Atrial Natriuretic Peptide (ANP) (1-28) treatment significantly alleviated colonic inflammation by inhibiting the STING pathway, reducing the expression of inflammatory cytokines such as TNF-α, IL-1β, IL-6, IFN-α, and IFN-β in colonic tissues and epithelial cells. Atrial Natriuretic Peptide (ANP) (1-28) also repaired gut barrier function by promoting the expression of tight junction proteins (ZO-1 and occludin) and inhibited ER stress-induced autophagy via the STING pathway[7]. Atrial Natriuretic Peptide (ANP) (1-28)(2.5µg/kg) was administered to wild-type mice via tail vein injection. Atrial Natriuretic Peptide significantly increased the levels of the autophagy marker LC3-II in the mouse heart and reduced infarct size in ischemia-reperfusion (I/R) injury[8].
References:
[1] Kohno M, Yokokawa K, Horio T, et al. Atrial and brain natriuretic peptides inhibit the endothelin-1 secretory response to angiotensin II in porcine aorta. Circ Res. 1992 Feb;70(2):241-7.
[2] Potter LR, Yoder AR, Flora DR, et al. Natriuretic peptides: their structures, receptors, physiologic functions and therapeutic applications. Handb Exp Pharmacol. 2009;(191):341-66.
[3] Santhekadur PK, Kumar DP, Seneshaw M, et al. The multifaceted role of natriuretic peptides in metabolic syndrome. Biomed Pharmacother. 2017 Aug;92:826-835.
[4] Sadoshima J, Jahn L, Takahashi T, et al. Molecular characterization of the stretch-induced adaptation of cultured cardiac cells. An in vitro model of load-induced cardiac hypertrophy. J Biol Chem. 1992 May 25;267(15):10551-60.
[5] Nakagawa H, Oberwinkler H, Nikolaev VO, et al. Atrial natriuretic peptide locally counteracts the deleterious effects of cardiomyocyte mineralocorticoid receptor activation. Circ Heart Fail. 2014 Sep;7(5):814-21.
[6] Tian X, Tian Y, Gawlak G, et al. Control of vascular permeability by atrial natriuretic peptide via a GEF-H1-dependent mechanism. J Biol Chem. 2014 Feb 21;289(8):5168-83.
[7] Chen C, Zhang Y, Tao M, et al. Atrial Natriuretic Peptide Attenuates Colitis via Inhibition of the cGAS-STING Pathway in Colonic Epithelial Cells. Int J Biol Sci. 2022 Feb 7;18(4):1737-1754.
[8] Forte M, Marchitti S, Di Nonno F, et al. NPPA/atrial natriuretic peptide is an extracellular modulator of autophagy in the heart. Autophagy. 2023 Apr;19(4):1087-1099.
Atrial Natriuretic Peptide (ANP) (1-28), human, porcine Acetate是一种生物活性肽，在身体的稳态机制中发挥着关键作用。Atrial Natriuretic Peptide (ANP) (1-28)以剂量依赖性方式抑制血管紧张素 II（angiotensin II）诱导的内皮素-1（endothelin-1）的分泌[1]。Atrial Natriuretic Peptide (ANP) (1-28)主要由心房肌细胞在心房扩张增加时分泌， 28个氨基酸序列在人的和猪的形式之间高度保守。乙酸盐的修饰可能在一定程度上影响其溶解度、稳定性和生物活性[2]。Atrial Natriuretic Peptide (ANP) (1-28)与其特定受体结合，主要是与鸟苷酸酰化酶连接的利钠肽受体-A（NPR-A），导致细胞内环鸟苷单磷酸（cGMP）水平增加，升高的cGMP随后介导一系列生理效应。在肾脏中，Atrial Natriuretic Peptide (ANP) (1-28)通过增加肾小球滤过率、抑制肾小管中的钠重吸收以及抑制肾素-血管紧张素-醛固酮系统（RAAS）促进利钠作用（增加钠的排泄）和利尿作用（增加尿液排出），这有助于减少血容量 [3]。Atrial Natriuretic Peptide (ANP) (1-28)导致血管扩张，减少外周血管阻力，从而降低血压。ANP对心脏也具有抗纤维化和抗肥大作用，帮助防止心脏重塑并维持正常的心脏功能[4]。
在体外，Atrial Natriuretic Peptide (ANP) (1-28)（10nmol/L）预处理人类胚胎肾细胞（HEK 293）30分钟，显著抑制了醛固酮（500pmol/L）诱导的矿化皮质激素受体（MR）的核转位[5]。Atrial Natriuretic Peptide (ANP) (1-28)（100nM）预处理人肺动脉内皮细胞（HPAECs）20分钟，显著抑制了凝血酶（0.5units/mL）诱导的内皮细胞通透性增加，Atrial Natriuretic Peptide (ANP) (1-28)通过Rac1-PAK1通路以剂量浓度依赖的方式抑制GEF-H1的活性，进而抑制Rho信号通路，减少肌球蛋白轻链（MLC）的磷酸化，抑制应力纤维的形成，从而减轻细胞收缩和通透性增加[6]。
在体内，Atrial Natriuretic Peptide (ANP) (1-28)（每只小鼠腹腔注射含有2µg ANP 的400µL PBS）被注射到患有DSS诱导的结肠炎的小鼠中。Atrial Natriuretic Peptide (ANP) (1-28)治疗通过抑制STING通路显著减轻了结肠炎症，降低了结肠组织和上皮细胞中炎症细胞因子（TNF-α、IL-1β、IL-6、IFN-α和IFN-β）的表达。ANP还通过促进紧密连接蛋白（ZO-1和occludin）的表达修复了肠道屏障功能，并通过STING通路抑制了内质网应激诱导的自噬[7]。Atrial Natriuretic Peptide (ANP) (1-28)（2.5µg/kg）通过尾静脉注射给予野生型小鼠。Atrial Natriuretic Peptide (ANP) (1-28)显著增加了小鼠心脏中的自噬标志物LC3-II水平，并在缺血再灌注（I/R）损伤中减少了梗死面积[8]。