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Natriuretic Peptides and Cardiac Function
Published in Malcolm J. Lewis, Ajay M. Shah, Endothelial Modulation of Cardiac Function, 2020
Kazuhiro Yamamoto, Margaret M. Redfield, John C. Burnett
Although the natriuretic family is known to be produced in the myocyte, it has been unclear whether the myocyte is a target for the natriuretic peptides. Recently, mRNAs for the three natriuretic peptide receptors have been demonstrated to be present in rat and human myocardial cells (Nunez, Dickson and Brown, 1992; Brown, Nunez and Wilkins, 1993; Lin et al., 1995), which suggests the presence of these receptors in myocardial cells. In the isolated normal myocardial cell, ANP and BNP stimulate generation of cGMP, however, CNP does not (Lin et al., 1995). Therefore, the heart is likely to be a target organ for ANP and BNP and these peptides may act as autocrine/paracrine factors in the heart affecting ventricular structure and function. These findings would support little function of NPR-B in normal myocardial cells and the role of CNP as a paracrine factor acting on the myocytes is unclear. Recent studies (Furuya et al., 1991; Porter et al., 1992; Wei et al., 1993) have demonstrated the endothelial-independent actions of CNP on the vascular smooth muscle cell and suggest the presence of NPR-B on the vascular smooth muscle cells and an autocrine/paracrine role of CNP in the regulation of vascular tone. Given these observations, CNP may affect ventricular function indirectly through its effects on coronary blood flow.
Appetite Control in C. elegans
Published in Ruth B.S. Harris, Appetite and Food Intake, 2017
Kristen Davis, Mi Cheong Cheong, Ji Su Park, Young-Jai You
The conservation of the signaling system at the molecular level is incredible; morphine induces pumping during starvation, mimicking the NLP-24 role in MC minus worms. The morphine effect on pumping is completely abolished in NPR-17 mutants, strongly suggesting that NPR-17 is the receptor that morphine acts on. Finally, heterologously expressed NPR-17 is activated by specific MOR-1 (loperamide) and KOR-1 (U69593) agonists used in mammals, and this activation is blocked by naloxone (Cheong et al. 2015). This proves that NPR-17 is an opioid receptor and NLP-24 is an endogenous opioid of C. elegans.
Therapeutic Effects and Immunomodulatory Activities of Natriuretic Peptides
Published in Sami I. Said, Proinflammatory and Antiinflammatory Peptides, 2020
Thomas Flüge, Markus Meyer, Wolf-Georg Forssmann
In order to compare the effects of various NPs, we analyzed the relaxation induced by CDD/ANP, URO, BNP, and CNP on guinea pig tracheal smooth muscle in vitro. In addition, we included phosphorylated derivatives, such as P-CDD/ANP and P-URO, in this investigation, because phosphorylation was shown to increase the NEP resistance of CDD/ANP (41). Carbachol was used to induce 80% of the maximum bronchoconstriction. After the tracheal tension reached a plateau, dose-response curves of the various peptides in the range of 5 × 1010 to 10-6 M were recorded. Isoproterenol was added at the end of each experiment to demonstrate the maximum relaxation. Results were calculated as a percentage of this maximum response. The statistical evaluation revealed highly significant differences in the relaxant effects of the different peptides (p < .0001, ANOVA, repeated measures). At 10-6 M, the rank order of potency was URO > P-URO > P-CCD = BNP ≥ CDD > CNP, which equaled a relaxant effect of between 65.8 ± 2.8% (SEM) and 13.2 ± 1.6% of the maximum possible relaxation for URO and CNP, respectively (Fig. 2) (88). These results reflect functional evidence for NPR-A receptors, but no importance of NPR-B-binding sites for the interaction of NPs with bronchial smooth muscle cells. In accordance with data on the vasorelaxant potency of P-URO compared to URO, a significant decrease in the URO effects on the guinea pig tracheal smooth muscle preparations was documented following phosphorylation (89). The diminution in relaxant activity of CDD/ANP after phosphorylation may be counter-balanced by the higher NEP resistance of P-CDD/ANP, because there was no significant difference between the two peptides.
Relevance of the assessment of natriuretic peptide plasma concentrations in hypertensive pregnant women
Published in Biomarkers, 2020
Agata Gondek, Aleksandra Jagodzińska, Bronisława Pietrzak, Artur Mamcarz, Agnieszka Cudnoch-Jędrzejewska
To date, three receptors for NPs have been identified: natriuretic peptide receptor A (NPR-A), B (NPR-B) and C (NPR-C) (Potter et al.2009). NPR-A and NPR-B have guanyl cyclase activity and as a result of their activation, intracellular synthesis of cyclic guanosine monophosphate (cGMP) occurs. In turn, NPR-C (a so-called clearance receptor) does not have such activity, and its main function is the local control of the concentration of NPs in the process of internalization and degradation dependent on the receptor. The NP receptors are characterized by selectivity: NPR-A mainly binds ANP and BNP, in turn NPR-B predominantly binds CNP, and NPR-C – with the highest affinity – binds ANP, followed by CNP and BNP. The most commonly occurring receptor for NPs is NPR-C, whose expression was detected in vascular endothelial cells and in the following organs: CNS, lungs, adrenal glands, kidney, heart and blood vessels. NPR-A expression was demonstrated, in the kidneys, lungs, adipose tissue, CNS, heart and blood vessels. In turn, NPR-B expression occurs, in the CNS, bones, fibroblasts, kidneys, uterus, heart and blood vessels (Fu et al.2018).
Incorporating molecular biomarkers into clinical practice for gastric cancer
Published in Expert Review of Anticancer Therapy, 2019
Shunsuke Nakamura, Mitsuro Kanda, Yasuhiro Kodera
Neuropilin 1 (NRP1) mediates the growth and metastasis of cancer cells through its function as a multifunctional coreceptor that interacts with the components of signaling pathways [57]. Although the oncogenic roles of NRP1 have been investigated, the correlation between NRP1 and prognosis of GC patients was still undefined in previous studies. Wang et al. [57]explored candidate biomarkers of DNA methylation using of two methylation array datasets and an RNA sequencing-based gene-profiling dataset. This study reveals that NPR1 is hypomethylated and upregulated in GC tissues. Further, univariate prognostic analysis of differentially expressed genes (DEGs) with altered methylation status shows that NPR1 is the most significant prognostic indicator of the outcomes of GC patients. The OS of patients with GC in low NRP1 expression is significantly longer compared with that of patients with high expression. Moreover, WGCNA analysis shows that NPR1 is strongly coexpressed with platelet-derived growth factor receptor beta (PDGFRB). High expression levels of NRP1 and PDGFRB are associated with the malignant phenotype of patients with GC, including Lauren histological diffuse type, higher histological grade, and poor prognosis [57]. These findings indicate that the expression of NRP1 and PDGFRB is significantly associated with aggressive phenotypes of GC and can predict the survival and prognosis of patients with GC.
The effects of valproic acid on the mRNA expression of Natriuretic Peptide Receptor A and KQT-like subfamily Q-1 in human colon cancer cell lines
Published in Alexandria Journal of Medicine, 2018
Mona Hajikazemi, Hoda Sohrabi, Ahad Yamchi, Mohsen Saeedi
NPR-A which is one of the specific receptors for ANP cardiac hormone is expressed in numerous human cancer cells including CRC.15,18 NPR-A is involved in different physiological and pathological processes and has been recently introduced as a novel anticancer target.20,32 However, there is no record available comparing the expression level of NPR-A among different human CRC cell lines.33 In order to target the CRC cell lines with the overexpression of NPR-A, we examined the expression of NPR-A among four different human CRC cell lines including HCT-116, SW-480, HT-29 and Caco-2. The lowest expression was demonstrated in HCT-116. The expression level of NPR-A was higher among SW-480 and HT-29 cells compared to HCT-116. We also quantified the expression of KCNQ1 gene among all CRC cell lines. Similar to the expression pattern of NPR-A, the mRNA expression of KCNQ1 was higher in SW-480 and HT-29 cells. Therefore, SW-480 and HT-29, with different molecular characteristics, were selected to be studied. These CRC cell lines could be appropriate in vitro models to investigate NPR-A mediated novel anticancer strategies. The expression of NPR-A was not statistically different in Caco-2 compared to HCT-116.