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Particulate guanylyl cyclase

Tomoko Ichiki, John C Burnett
With the discovery of atrial natriuretic peptide (ANP), the heart as an endocrine organ was established. Basic science revealed that ANP, through the particulate guanylyl cyclase A receptor and cGMP, plays a fundamental role in cardiorenal biology. This work has led to the development of ANP as a therapeutic, especially in heart failure (HF). Human genomics has strengthened our understanding of ANP, revealing specific ANP gene variants that may be associated with biological dysfunction, but also may mediate protective properties, including in metabolic syndrome...
May 27, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
Laura M G Meems, John C Burnett
Endogenous natriuretic peptides serve as potent activators of particulate guanylyl cyclase receptors and the second messenger cGMP. Natriuretic peptides are essential in maintenance of volume homeostasis, and can be of myocardial, renal and endothelial origin. Advances in peptide engineering have permitted the ability to pursue highly innovative drug discovery strategies. This has resulted in designer natriuretic peptides that go beyond native peptides in efficacy, specificity, and resistance to enzymatic degradation...
December 2016: JACC. Basic to Translational Science
Kim C Jonas, Timothy Melrose, Iain R Thompson, Gary F Baxter, Victoria J Lipscomb, Stijn J Niessen, Charlotte Lawson, Craig A McArdle, Mark S Roberson, Imelda M McGonnell, Caroline P Wheeler-Jones, Robert C Fowkes
The natriuretic peptides, Atrial-, B-type and C-type natriuretric peptides (ANP, BNP, CNP), are regulators of many endocrine tissues and exert their effects predominantly through the activation of their specific guanylyl cyclase receptors (GC-A and GC-B) to generate cGMP. Whereas cGMP-independent signalling has been reported in response to natriuretic peptides, this is mediated via either the clearance receptor (Npr-C) or a renal-specific NPR-Bi isoform, which both lack intrinsic guanylyl cyclase activity. Here, we report evidence of GC-B-dependent cGMP-independent signalling in pituitary GH3 cells...
April 27, 2017: Cell and Tissue Research
Takeshi Kinoshita, Masashi Tawa, Tomoaki Suzuki, Yoshinari Aimi, Tohru Asai, Tomio Okamura
BACKGROUND: Spasm of arterial grafts is still a clinical problem in coronary artery bypass surgery. The present study was designed to examine the effect of particulate guanylyl cyclase activator (carperitide) as an antispastic agent in internal thoracic artery and gastroepiploic artery grafts. METHODS: Isolated arterial grafts taken during surgery were studied in organ bath in three ways: the relaxing effect of carperitide on vasoconstrictor-induced precontraction; the inhibitory effect of pretreatment with carperitide on subsequent vasoconstrictor-induced contraction; and the effect of carperitide and nitroglycerin on increase of intracellular cyclic guanosine monophosphate levels...
January 19, 2017: Annals of Thoracic Surgery
Johann Wojta
No abstract text is available yet for this article.
April 2016: European Heart Journal. Cardiovascular Pharmacotherapy
Candace Y W Lee, Brenda K Huntley, Daniel J McCormick, Tomoko Ichiki, S Jeson Sangaralingham, Ondrej Lisy, John C Burnett
AIMS: Cenderitide is a novel dual natriuretic peptide (NP) receptor chimeric peptide activator, which targets the particulate guanylyl cyclase B (pGC-B) receptor and pGC-A unlike native NPs. Cenderitide was engineered to retain the anti-fibrotic properties of C-type natriuretic peptide (CNP)/pGC-B with renal-enhancing actions facilitated by fusion to the carboxyl terminus of Dendroaspis NP (DNP), a pGC-A agonist, to CNP. Here, we address significance of the DNP carboxyl terminus in dual pGC receptor activation and actions of cenderitide compared with CNP on renal function and cyclic guanosine monophosphate (cGMP) in vivo and ex vivo in normal canines...
April 2016: European Heart Journal. Cardiovascular Pharmacotherapy
Marjorie Barrier, Marc-Antoine Bégorre, Isabelle Baudrimont, Mathilde Dubois, Véronique Freund-Michel, Roger Marthan, Jean-Pierre Savineau, Bernard Muller, Arnaud Courtois
Particulate air pollution exerts deleterious effects on cardiovascular system. We previously described that exposure to urban particulate matter (SRM1648) impairs nitric oxide (NO, a major vasculoprotective factor) responsiveness in intrapulmonary arteries. As Heme Oxygenase-1 (HO-1) is induced by urban particles in some cell types and is known to alter NO-dependent signaling pathway, the objective was to characterize HO-1 involvement in SRM1648-induced impairment of NO-dependent relaxation in intrapulmonary arteries...
April 2016: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Motahareh Moghtadaei, Iuliia Polina, Robert A Rose
Natriuretic peptides (NPs) are a family of cardioprotective hormones with numerous beneficial effects in cardiovascular system. The NP family includes several peptides including atrial NP (ANP), B-type NP (BNP), C-type NP (CNP) and Dendroaspis NP (DNP). These peptides elicit their effects by binding to three distinct cell surface receptors called natriuretic peptide receptors A, B and C (NPR-A, NPR-B and NPR-C). NPR-A (which binds ANP, BNP and DNP) and NPR-B (which is selective for CNP) are particulate guanylyl cyclase (GC)-linked receptors that mediate increases in cGMP upon activation...
January 2016: Progress in Biophysics and Molecular Biology
Chang Ho Lee, Gi Won Ha, Jong Hun Kim, Suhn Hee Kim
BACKGROUND: Renin-angiotensin system is involved in the pathophysiology of colonic inflammation. However, there are a few reports about modulation of natriuretic peptide system. AIMS: This study investigates whether a local atrial natriuretic peptide (ANP) system exists in rat colon and whether ANP plays a role in the regulation of colonic motility in experimental colitis rat model. METHODS: Experimental colitis was induced by an intake of 5 % dextran sulfate sodium (DSS) dissolved in tap water for 7 days...
April 2016: Digestive Diseases and Sciences
Małgorzata Mitkiewicz
Guanylyl cyclase type A (GC-A) belongs to the particulate guanylyl cyclases (pGC), which, like the soluble guanylyl cyclases (sGC), catalyze the synthesis of a common secondary messenger, namely cyclic GMP (cGMP), involved in many cellular processes. Although both forms of guanylyl cyclases produce the same secondary messenger, activation of each of them triggers different signaling pathways leading to different cellular effects. This indicates that the final effect of cGMP depends on the site of its synthesis in the cell (cytosol or cell membrane)...
April 9, 2015: Postȩpy Higieny i Medycyny Doświadczalnej
L Breivik, A Jensen, S Guvåg, E K Aarnes, A Aspevik, E Helgeland, S Hovland, T Brattelid, A K Jonassen
Exogenously administered B-type natriuretic peptide (BNP) has been shown to offer cardioprotection through activation of particulate guanylyl cyclase (pGC), protein kinase G (PKG) and KATP channel opening. The current study explores if cardioprotection afforded by short intermittent BNP administration involves PI3K/Akt/p70s6k dependent signaling, and whether this signaling pathway may participate in regulation of BNP mRNA expression at early reperfusion. Isolated Langendorff perfused rat hearts were subjected to 30min of regional ischemia and 120min of reperfusion (IR)...
April 2015: Peptides
Robert Lukowski, Thomas Krieg, Sergei D Rybalkin, Joseph Beavo, Franz Hofmann
cGMP inhibits hypertrophy, decreases fibrosis, and protects against cardiac ischemia-reperfusion (I/R) injury. Gene-targeting studies have not defined a clear role for its major downstream effector, cGMP-dependent protein kinase I (cGKI), in cardiac hypertrophy, but do implicate cGMP-cGKI signaling in fibrosis and I/R injury. No direct cGKI activators have advanced to clinical trials, whereas cardiac trials of agents that modulate cGMP via particulate or soluble guanylyl cyclases (GCs) and phosphodiesterase 5 (PDE5) are ongoing...
August 2014: Trends in Pharmacological Sciences
Paul M McKie, Alessandro Cataliotti, Tomoko Ichiki, S Jeson Sangaralingham, Horng H Chen, John C Burnett
BACKGROUND: Systemic hypertension is a common characteristic in acute heart failure (HF). This increasingly recognized phenotype is commonly associated with renal dysfunction and there is an unmet need for renal enhancing therapies. In a canine model of HF and acute vasoconstrictive hypertension we characterized and compared the cardiorenal actions of M-atrial natriuretic peptide (M-ANP), a novel particulate guanylyl cyclase (pGC) activator, and nitroglycerin, a soluble guanylyl cyclase (sGC) activator...
January 2, 2014: Journal of the American Heart Association
Iain R Thompson, Samantha M Mirczuk, Lorna Smith, Andrew J Lessey, Bigboy Simbi, Andrew Sunters, Gary F Baxter, Victoria J Lipscomb, Imelda M McGonnell, Caroline P Wheeler-Jones, Abir Mukherjee, Mark S Roberson, Craig A McArdle, Robert C Fowkes
The guanylyl cyclases, GC-A and GC-B, are selective receptors for atrial and C-type natriuretic peptides (ANP and CNP, respectively). In the anterior pituitary, CNP and GC-B are major regulators of cGMP production in gonadotropes and yet mouse models of disrupted CNP and GC-B indicate a potential role in growth hormone secretion. In the current study, we investigate the molecular and pharmacological properties of the CNP/GC-B system in somatotrope lineage cells. Primary rat pituitary and GH3 somatolactotropes expressed functional GC-A and GC-B receptors that had similar EC50 properties in terms of cGMP production...
February 2014: Cell and Tissue Research
Rebecca M Perrett, Craig A McArdle
Gonadotropin-releasing hormone (GnRH) is the primary regulator of mammalian reproductive function in both males and females. It acts via G-protein coupled receptors on gonadotropes to stimulate synthesis and secretion of the gonadotropin hormones luteinizing hormone and follicle-stimulating hormone. These receptors couple primarily via G-proteins of the Gq/ll family, driving activation of phospholipases C and mediating GnRH effects on gonadotropin synthesis and secretion. There is also good evidence that GnRH causes activation of other heterotrimeric G-proteins (Gs and Gi) with consequent effects on cyclic AMP production, as well as for effects on the soluble and particulate guanylyl cyclases that generate cGMP...
November 20, 2013: Frontiers in Endocrinology
Hai-Kang Zhao, Bao-Ying Chen, Rui Chang, Jian-Bang Wang, Feng Ni, Lei Yang, Xi-Chao Dong, Shu-Hu Sun, Ge Zhao, Wei Fang, Quan-Rui Ma, Xue-Lian Wang, Jun Yu
Vasonatrin peptide (VNP), a novel manmade natriuretic peptide, is known as a cardiovascular active substance. However, its neuroeffects are largely unknown. Here, cultured dopaminergic neurons from ventral mesencephalon of mouse were exposed to N-methyl-4-phenylpyridinium (MPP(+)), and the effects of VNP on the neurotoxicity of MPP(+) were investigated. As a result, MPP(+) caused injuries in the dopaminergic neurons. VNP significantly reduced the cytotoxicity of MPP(+) by increasing axon number and length of dopaminergic neurons, and by enhancing the cell viability...
November 2013: Peptides
Kerstin Y Beste, Corinna M Spangler, Heike Burhenne, Karl-Wilhelm Koch, Yuequan Shen, Wei-Jen Tang, Volkhard Kaever, Roland Seifert
Guanylyl cyclases (GCs) regulate many physiological processes by catalyzing the synthesis of the second messenger cGMP. The GC family consists of seven particulate GCs (pGCs) and a nitric oxide-activated soluble GC (sGC). Rat sGC α1β1 possesses much broader substrate specificity than previously assumed. Moreover, the exotoxins CyaA from Bordetella pertussis and edema factor (EF) from Bacillus anthracis possess nucleotidyl cyclase (NC) activity. pGC-A is a natriuretic peptide-activated homodimer with two catalytic sites that act cooperatively...
2013: PloS One
Sabine Weninger, Joris H De Maeyer, Romain A Lefebvre
Our objective was to investigate the role of phosphodiesterase (PDE)3 and PDE4 and cGMP in the control of cAMP metabolism and of phosphorylation of troponin I (TnI) and phospholamban (PLB) when 5-HT4 receptors are activated in pig left atrium. Electrically paced porcine left atrial muscles, mounted in organ baths, received stimulators of particulate guanylyl cyclase (pGC) or soluble guanylyl cyclase (sGC) and/or specific PDE inhibitors followed by 5-HT or the 5-HT4 receptor agonist prucalopride. Muscles were freeze-clamped at different moments of exposure to measure phosphorylation of the cAMP/protein kinase A targets TnI and PLB by immunoblotting and cAMP levels by enzyme immunoassay...
August 2013: Naunyn-Schmiedeberg's Archives of Pharmacology
Alessandra Borgognone, Kate L Lowe, Stephen P Watson, Melanie Madhani
Cyclic guanosine-3',5'-monophoshate (cGMP) is the common second messenger for the cardiovascular effects of nitric oxide (NO) and natriuretic peptides (NP; e.g. atrial NP [ANP]), which activate soluble and particulate guanylyl cyclases, respectively. The role of NO in regulating cGMP and platelet function is well documented, whereas there is little evidence supporting a role for NPs in regulating platelet reactivity. By studying platelet aggregation and secretion in response to a PAR-1 peptide, collagen and ADP, and phosphorylation of the cGMP-dependent protein kinase (PKG) substrate vasodilator-stimulated phosphoprotein (VASP) at serine 239, we evaluated the effects of NPs in the absence or presence of the non-selective cGMP and cAMP phosphodiesterase (PDE) inhibitor, 3-isobutyl-1-methylxanthine (IBMX)...
2014: Platelets
Frank Wunder, Annette Woermann, Andreas Geerts, Markus Milde
Receptor guanylyl cyclases are implicated in a growing number of pathophysiologies and, therefore, represent an important target class for drug development. We report here the generation and pharmacological characterization of three particulate guanylyl cyclase (pGC) reporter cell lines. Plasmid constructs encoding the natriuretic peptide receptors GC-A and GC-B, and the heat-stable enterotoxin receptor GC-C, were stably transfected in a parental reporter cell line expressing a cyclic nucleotide-gated (CNG) cation channel, acting as the biosensor for intracellular cGMP...
January 5, 2013: European Journal of Pharmacology
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