1. Functional and pharmacological characterization of the natriuretic peptide-dependent lipolytic pathway in human fat cells
Jean Galitzky, Cedric Moro, François Crampes, Max Lafontan, Coralie Sengenes, Michel Berlan J Pharmacol Exp Ther . 2004 Mar;308(3):984-92. doi: 10.1124/jpet.103.060913.
A lipolytic pathway involving natriuretic peptides has recently been discovered in human fat cells. Its functional characteristics and the interactions of the atrial natriuretic peptide (ANP)-induced effects with adrenergic and insulin pathways were studied. Characterization of the action of ANP antagonists, i.e., A71915, anantin, S-28-Y (Ser-28-Tyr, a synthesized peptide), and HS-142-1 (a microbial polysaccharide), was performed. Lipolytic assays and intracellular cGMP and cAMP determinations were performed on isolated fat cells. Cell membranes were used for binding studies. At low concentrations ANP and isoproterenol [beta-adrenergic receptor (beta-AR) agonist] exerted additive lipolytic effects. The alpha(2)-AR pathway did not interfere with that of ANP. Lipolytic effects of ANP were unaltered by a 2-h pretreatment of fat cells with insulin, whereas beta-AR-induced lipolysis was reduced. Homologous desensitization occurred for ANP-dependent lipolytic pathways. Dendroapsis natriuretic peptide exhibited a similar maximal effect but a 10-fold higher lipolytic potency than ANP and mini-ANP (the shortest form of ANP). The antagonist A71915 exhibited competitive antagonistic properties with a pA(2) value of 7.51. Anantin displayed noncompetitive antagonism and exerted an inhibitory action on basal and beta-adrenergic receptor-induced lipolytic response. S-28-Y exhibited antagonist potencies toward ANP-induced lipolysis and behaved as a partial lipolytic agonist with a lower pD(2) value (7.4 +/- 0.2) than ANP (9.4 +/- 0.3). HS-142-1 exerted the weakest antagonistic effects. The results demonstrate that ANP-dependent effects do not interfere with beta- and alpha(2)-adrenergic pathways in human fat cells. They are unaffected by insulin pretreatments of fat cells but undergo desensitization. In the search of potent and specific natriuretic peptide receptor-A antagonist, in the human fat cell, A71915 was the only reliable one found.
2. The potential role of atrial natriuretic peptide in the effects of Angiotensin-(1-7) in a chronic atrial tachycardia canine model
Jian Li, Guangping Li, Jun Zhao, Enzhao Liu, Tiecheng Liu, Lingshan Qi J Renin Angiotensin Aldosterone Syst . 2016 Mar 23;17(1):1470320315627409. doi: 10.1177/1470320315627409.
Objective:The objective of this article is to investigate the possible role of atrial natriuretic peptide (ANP) in Angiotensin-(1-7) (Ang-(1-7)) signaling pathway on atrial electrical and structural remodeling in a chronic rapid atrial pacing canine model.Methods:Twenty-four dogs were randomly assigned to four groups: a sham group, paced control group, a paced + Ang-(1-7) group and a paced + Ang-(1-7) + A-71915 group. Atrial rapid pacing (ARP) at 600 bpm was maintained for 14 days except in the animals from the sham group. During the pacing, Ang-(1-7) (6 μg·kg-1·h-1) or Ang-(1-7) (6 μg·kg-1·h-1) + A-71915 (ANP receptor antagonist, 0.30 μg·kg-1·h-1) were given intravenously, respectively. After pacing, it was measured that electrophysiological parameters including atrial effective refractory periods (ERPs), inducibility and duration of atrial fibrillation (AF), ICaL and INa changed, where ICaL refers to voltage-dependent L-type Ca(2+) current and INa refers to cardiac sodium current. Then, the fibrosis and the expression of Cav1.2, INav1.5α subunit, TGF-β1 and ANP in atria were assessed.Results:After ARP, compared with the sham group, the atrial ERPs at six sites in each dog were shortened with the increasing in inducibility and duration of AF in the paced control group. The density of ICaL, INa and the expression of Cav1.2, INav1.5α subunit mRNA were decreased. Atrial tissue from the paced dogs showed significant interstitial fibrosis. The expression of TGF-β1 and ANP in mRNA and protein levels were increased. Compared with the paced control group, the shortening of atrial ERPs, and the increasing of inducibility and duration of AF induced by ARP were alleviated by Ang-(1-7) treatment (p < 0.05). The density of ICaL and INa and the expression of Cav1.2 and INav1.5α subunit mRNA were slightly decreased. Atrial tissue showed less interstitial fibrosis after Ang-(1-7) treatment. The increasing of ANP expression was improved by Ang-(1-7), while the increasing of TGF-β1 expression was alleviated by Ang-(1-7) (p < 0.05). A-71915 treatment blocked the beneficial effects of Ang-(1-7) on the aforementioned electrophysiological parameters and atrial fibrosis. And A-71915 treatment blocked Ang-(1-7), improving the expression of TGF-β1.Conclusion:Ang-(1-7) prevented atrial structural and electrical remodeling induced by ARP. Furthermore, Ang-(1-7) promoted ANP secretion, and ANP played a crucial role in the cardiac protection of the former.
3. Effects of endothelin family on ANP secretion
Kyung Woo Cho, Kuichang Yuan, Young Tae Choi, Jong Hun Kim, Suhn Hee Kim, Byung Mun Park Peptides . 2016 Aug;82:12-19. doi: 10.1016/j.peptides.2016.05.007.
The endothelins (ET) peptide family consists of ET-1, ET-2, ET-3, and sarafotoxin (s6C, a snake venom) and their actions appears to be different among isoforms. The aim of this study was to compare the secretagogue effect of ET-1 on atrial natriuretic peptide (ANP) secretion with ET-3 and evaluate its physiological meaning. Isolated nonbeating atria from male Sprague-Dawley rats were used to evaluate stretch-activated ANP secretion in response to ET-1, ET-2, ET-3, and s6C. Changes in mean blood pressure (MAP) were measured during acute injection of ET-1 and ET-3 with and without natriuretic peptide receptor-A antagonist (A71915) in anesthetized rats. Changes in atrial volume induced by increased atrial pressure from o to 1, 2, 4, or 6cm H2O caused proportional increases in mechanically-stimulated extracellular fluid (ECF) translocation and stretch-activated ANP secretion. ET-1 (10nM) augmented basal and stretch-activated ANP secretion in terms of ECF translocation, which was blocked by the pretreatment with ETA receptor antagonist (BQ123, 1μM) but not by ETB receptor antagonist (BQ788, 1μM). ETA receptor antagonist itself suppressed stretch-activated ANP secretion. As compared to ET-1- induced ANP secretion (3.2-fold by 10nM), the secretagogue effects of ANP secretion by ET-2 was similar (2.8-fold by 10nM) and ET-3 and s6C were less potent (1.7-fold and 1.5-fold by 100nM, respectively). Acute injection of ET-1 or ET-3 increased mean blood pressure (MAP), which was augmented in the presence of natriuretic peptide receptor-A antagonist. Therefore, we suggest that the order of secretagogue effect of ET family on ANP secretion was ET-1≥ET-2>>ET-3>s6C and ET-1-induced ANP secretion negatively regulates the pressor effect of ET-1.
