• The lcn2-induced phenotypic changes of astrocytes occurred through a Rho-ROCK (Rho kinase)-GFAP pathway, which was positively regulated by nitric oxide and cGMP. (jneurosci.org)
  • The whole pattern of reactions begins with the activation of nerve fibers in the parasympathetic system which, through nitric oxide (NO) and cGMP, its secondary messenger, initiate the described cascade. (selfgrowth.com)
  • Most of the effects of the signaling molecule nitric oxide (NO) are mediated by cGMP, which is synthesized by soluble guanylyl cyclase and degraded by phosphodiesterases. (rupress.org)
  • The effects of MB are apparent only in the case of nitric oxide (NO) up-regulation, and it is not a vasoconstrictor per se. (biomedcentral.com)
  • Inhibitors of phosphodiesterase-5 (PDE 5 ) are a class of drug that were originally developed as anti-ischaemic agents based on their ability to overexpress the nitric oxide (NO) pathway pursued via cyclic guanosine monophosphate (cGMP) signalling. (ecrjournal.com)
  • cGMP is also produced in response to hormones, such as nitric oxide and atrial natriuretic peptide, which leads to the relaxation of vascular smooth muscle and is thus important for regulation of blood pressure [ 1 ]. (biomedcentral.com)
  • Examples of second messengers are cyclic adenosine monophosphate (cAMP), calcium ions, nitric oxide, cyclic guanosine monophosphate (cGMP) and phospholipids. (bscb.org)
  • Hydrolysis of cAMP by PDE3 isoforms is also directly inhibited by cGMP, although PDE3B is only ≈10% as sensitive to cGMP inhibition as PDE3A. (wikipedia.org)
  • Inhibition by specific antagonists indicates that continuing activation of cAMP-PKA and cGMP-PKG pathways is required to maintain hyperexcitability after dissociation. (nih.gov)
  • Cumulative evidence indicates that NO/cGMP inhibition would make a difference in vasoplegia treatment. (biomedcentral.com)
  • Our research programs have been among the pioneers in elucidating the function, regulation, and underlying mechanism of different PDE activation/ inhibition in the pathogenesis of cardiovascular diseases. (rochester.edu)
  • 6 in the rat aorta, vardenafil but not sildenafil or tadalafil affects serum calcium (Ca++) handling to produce relaxation in addition to the typical increase of cGMP mediated by PDE 5 inhibition. (ecrjournal.com)
  • Here we show that in platelets and aortic tissue, NO led to a biphasic response characterized by a tremendous increase in cGMP (up to 100-fold) in less than 30 s and a rapid decline, reflecting the tightly controlled balance of guanylyl cyclase and phosphodiesterase activities. (rupress.org)
  • Over the years multiple mechanisms of regulation of GC-C activity has been identified including allosteric controlled by various domains in the receptor and phosphorylation-mediated regulation of guanylyl cyclase activity. (iisc.ac.in)
  • It took another decade to establish that cGMP and the enzyme responsible for its synthesis, guanylyl cyclase, are also present in mammalian tissues. (biomedcentral.com)
  • It is believed that the core contains common structural elements that are important for the hydrolysis of cAMP and cGMP phosphodiester bonds. (wikipedia.org)
  • Cyclic nucleotide phosphodiesterases (PDEs) play a role in signal transduction by regulating intracellular cyclic nucleotide concentrations through hydrolysis of cAMP and/or cGMP to their respective nucleoside 5-prime monophosphates. (thermofisher.com)
  • We will group genes into pathways to identify likely targets of Rv3651 regulation. (ssgcid.org)
  • Thus, our discovery of the role of functional interaction between intracellular signaling pathways mediated by calcium ions (Ca 2+) and cyclic adenosine monophosphate (cAMP) (Ca 2+ /cAMP signaling interaction) in these cellular responses, opened a great avenue for the development of new antitumor therapeutic strategies. (researchgate.net)
  • Recent results indicate that after chronic compression of DRG (CCD treatment), both hyperexcitability of neurons in intact DRG and behaviorally expressed hyperalgesia are maintained by concurrent activity in cAMP-protein kinase A (PKA) and cGMP-protein kinase G (PKG) signaling pathways. (nih.gov)
  • Both forms of injury increase the electrophysiological responsiveness of the neurons to activation of cAMP-PKA and cGMP-PKG pathways as indicated by enhancement of hyperexcitability by agonists of these pathways in dissociated or CCD-treated neurons but not in control neurons. (nih.gov)
  • Although inflammatory signals are known to activate cAMP-PKA pathways, dissociation-induced hyperexcitability is unlikely to be triggered by signals released from inflammatory cells recruited to the DRG because of insufficient time for recruitment during the dissociation procedure. (nih.gov)
  • These results suggested that the cAMP-dependent pathway, which is independent of MAPK pathways, plays a negative role in γ-globin gene expression in K562 cells. (elsevierpure.com)
  • Our results suggest that MEPY exerts its vasorelaxant effects via the activation of NO formation by means of l -Arg and NO-cGMP pathways and via the blockage of extracellular Ca 2+ channels. (biomedcentral.com)
  • Activation of PDE3B decreases concentrations of cAMP, which in turn reduces protein kinase A activity. (wikipedia.org)
  • By monitoring the phosphate rearrangement during cGMP and pyrophosphate formation in light-activated RGC, we were able to confirm the M state as the active state of the protein. (elifesciences.org)
  • This Rho protein is phosphorylated in vitro on serine 188 by cAMP- and cGMP-dependent kinases (PKA and PKG). (phosphosolutions.com)
  • The levels of phosphorylation of mitogen-activated protein kinases (MAPKs) were not affected by the cAMP-dependent pathway. (elsevierpure.com)
  • Doublecortin-like kinase protein 1 (DCLK1) is a multifunctional protein kinase involved in the regulation of cell proliferation, differentiation, survival, and migration. (bvsalud.org)
  • Activation of GC-C by these ligands results in an increase in intracellular cGMP levels, which then activates cGMP-dependent protein kinase and cross-activates protein kinase A. In turn, these activated kinases phosphorylate and active the cystic fibrosis transmembrane conductance regulator (CFTR), resulting in chloride and water secretion into the intestine lumen, thus regulating salt and water homeostasis in the intestine. (iisc.ac.in)
  • The patch-clamp method was employed to establish the mechanism of regulation by guanosine 3',5'-cyclic monophosphate (cGMP)dependent protein kinase (PKG) of large Ca 2+ -activated K + channels (BK(Ca)) in human mesangial cells. (nebraska.edu)
  • Activation by cGMP plus MgATP was blocked by KT-5823, an inhibitor of PKG, but not by KT-5720, an inhibitor of cAMP-dependent protein kinase (PKA). (nebraska.edu)
  • Stockand, JD & Sansom, SC 1996, ' Mechanism of activation by cGMP-dependent protein kinase of large Ca 2+ -activated K + channels in mesangial cells ', American Journal of Physiology - Cell Physiology , vol. 271, no. 5 40-5, pp. (nebraska.edu)
  • Suggestion of a role for protein phosphorylation in the regulation of intestinal active NaCl transport was found by studying the effects of low concentrations of promethazine on Ca 2+ -calmodulin (CaM)-dependent protein phosphorylation of ileal microvillus membranes and on active ileal electrolyte transport. (johnshopkins.edu)
  • Activation of cAMP protein kinase A (PKA) stimulates pigmentation through cAMP response element binding protein (CREB) dependent upregulation of MITF expression ( Rodríguez and Setaluri, 2014 ). (frontiersin.org)
  • As in somatic cells, sperm intracellular cAMP concentration is regulated by the opposite action of two enzymes: the adenylyl cyclases (AC), which synthesize cAMP from ATP, and the phosphodiesterases (PDE), which break the phosphodiester bond of cAMP to form 5'-adenosine monophosphate (AMP). (plos.org)
  • Phosphodiesterases (PDEs) hydrolyze the phosphodiester bond of cAMP and cGMP to form the inactive 5′-AMP and 5′-GMP. (biomedjournal.com)
  • In addition to its PRKA-dependent effects, different studies have clearly demonstrated that cAMP also activates EPAC ( E xchange P roteins directly A ctivated by c AMP) during capacitation and acrosome exocytosis [ 15 - 17 ]. (plos.org)
  • Although cGMP activates the cyclic AMP (cAMP)-dependent pathway by suppressing cGMP-inhibited phosphodiesterase 3 (PDE3), the effects of the cAMP-dependent pathway on γ-globin gene expression are unknown. (elsevierpure.com)
  • cAMP signaling pathway is a common functional pathway of signal transduction in Prokaryota and in Eukaryota. (am-online.org)
  • Participation of cAMP signaling pathway in the regulation of metabolic processes in cyanobacteria cells has been demonstrated by the studies showing a distinct response of these organisms to exogenous cAMP in the medium. (am-online.org)
  • In these organisms the presence of cAMP synthesis and degradation enzymes (AC and PDE, respectively) was demonstrated and genes encoding proteins involved in signal transduction pathway of cAMP were identified. (am-online.org)
  • Currently the sequences of 29 complete genomes of different species of cyanobacteria (and their strains) are known in which different genes connected with cAMP pathway have been identified. (am-online.org)
  • Current studies of cAMP signaling pathway in cyanobacteria may indicate that it is not a universal pathway regulating cell functioning in the genomes of some cyanobacteria AC, PDE, CRP genes and genes whose activity is regulated by CRP were not detected. (am-online.org)
  • However, there is a possibility that their genomes may contain modified, not yet identified sequences encoding individual elements of the cAMP pathway. (am-online.org)
  • cGMP signaling pathway in cyanobacteria. (am-online.org)
  • Role of cAMP pathway in the reaction to environmental factors and in the regulation of cell growth of cyanobacteria. (am-online.org)
  • Regulation of transcription in cyanobacteria by cAMP signaling pathway. (am-online.org)
  • Fetal hemoglobin inducers such as hemin, butyrate, and hydroxyurea stimulate γ-globin gene expression by activating the cyclic GMP (cGMP)-dependent pathway. (elsevierpure.com)
  • The cAMP-dependent pathway was activated in K562 cells using the adenylate cyclase activator forskolin. (elsevierpure.com)
  • The cAMP-dependent pathway was found to be activated in K562 cells in which the cGMP-dependent pathway was activated by hemin. (elsevierpure.com)
  • Activation of the cAMP-dependent pathway by forskolin inhibited hemin-induced expression of γ-globin mRNA and decreased transcriptional activity of the γ-globin gene promoter. (elsevierpure.com)
  • The GC-C mediated cGMP signal transduction pathway also maintains intestinal crypt-villus axis homeostatis by exerting a cytostatic effect on the epithelial cells, there by regulating their turn over. (iisc.ac.in)
  • However, later on the clinical applicability of the enhanced NO/cGMP pathway in terms of inhibiting PDE 5 activity was felt to be more relevant than previously thought. (ecrjournal.com)
  • Cyclic nucleotides are intracellular second messengers involved in a plethora of functions from the ancestral fight-or-flight response to control or memory formation, from regulation of inflammation and immunity to the modulation of metabolism. (ox.ac.uk)
  • We are investigating the role of phosphodiesterases, the enzymes that degrade cyclic nucleotides, in the regulation of compartmentalized signaling and their involvement in heart disease. (ox.ac.uk)
  • During this process, second messengers such as cyclic nucleotides, cAMP and cGMP, are produced which serve to amplify the signal. (iisc.ac.in)
  • cAMP controls the activation of the initial voltage-gated state of the action potential, configuring nerve impulse, transcription-plasticity mechanism and long-term memory. (novapublishers.com)
  • DNA-dependent RNA polymerase activation is inducible, expressed under the conditions of adaptive value by cAMP. (novapublishers.com)
  • Such scheme of regulation of oocyte meiotic resumption is discussed (considered): the ac-tion of gonadotrophins, FSH and LH, causes increase the pro-duction of cAMP and subsequent activation of MAPK. (kiev.ua)
  • Sperm intracellular cAMP levels depend on the activity of adenylyl cyclases, mostly SACY, though transmembrane-containing adenylyl cyclases are also present, and on the activity of cyclic nucleotide phosphodiesterases (PDE) whose role is to degrade cAMP into 5'-AMP. (plos.org)
  • cAMP, which was originally identified by its ability to cause breakdown of glycogen in response to adrenaline, is produced by adenylyl cyclase, an enzyme first characterized in 1958. (biomedcentral.com)
  • Most mammalian adenylyl cyclases are large transmembrane proteins and subject to complex regulation, most importantly through direct interactions with heterotrimeric GTP-binding (G) proteins (Figure 2 , left-hand side). (biomedcentral.com)
  • PDE10A contributes to the regulation of the intracellular levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). (northwestern.edu)
  • The homeostatic role of phosphodiesterases (PDEs) as related to the intracellular levels of cAMP and cGMP was first described by Sutherland (Sutherland, Rall, 1958) who, due to this, was awarded the Nobel Prize for Physiology and Medicine in 1971. (biomedjournal.com)
  • In optimization of the intracellular levels of cAMP and cGMP, breakdown is predominant over synthesis. (biomedjournal.com)
  • Your second year builds on this knowledge and covers areas such as gene regulation, cell biology and metabolism. (kent.ac.uk)
  • Cyclic AMP (cAMP) and cGMP regulate a myriad of cellular functions, such as metabolism, contractility, motility, and transcription in virtually all cell types, including those of the cardiovascular system. (aspetjournals.org)
  • In mammals, adenosine 3', 5'-cyclic monophosphate (cAMP) is known to play highly important roles in sperm motility and acrosomal exocytosis. (plos.org)
  • Fertel and Weiss, 1976) therefore preventing the inactivation of the intracellular second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) by the respective PDE subtype(s). (biomedjournal.com)
  • PDE 5 comprises an enzyme superfamily with 11 subfamilies that hydrolyse the phosphodiester bond of cGMP and cyclic adenosine monophosphate (cAMP) to form the inactive 5'-GMP and 5'-AMP. (ecrjournal.com)
  • Cyclic guanosine monophosphate (cGMP) is a critical second messenger that regulates cardiovascular function and vision in humans. (biomedcentral.com)
  • cAMP and cGMP regulate a wide variety of cardiac functions, from the short-term effects on myocyte contraction/ relaxation to long-term effects such as gene expression and structural remodeling ( Figure 2 ). (rochester.edu)
  • Considerably higher resistance against cyclic nucleotide phosphodiesterases compared to dibutyryl or 8-Br-cAMP, no metabolic side effects. (biolog.de)
  • Dibutyryl cGMP (DBcGMP) significantly increased open probability (P(o)) of BK(Ca) in the absence but not in the presence of staurosporine in cell-attached patches. (nebraska.edu)
  • Phosphodiesterase 5 itself is an enzyme responsible for the breakdown of cGMP and cAMP nucleotides, which are messengers in the mechanism of action of many neurohormones. (selfgrowth.com)
  • Furthermore, this increase in cGMP degradation is paralleled by the phosphorylation of phosphodiesterase type 5 at Ser-92. (rupress.org)
  • Thus, our data suggest that NO-induced desensitization of the cGMP response is caused by the phosphorylation and subsequent activity increase of phosphodiesterase type 5. (rupress.org)
  • Two recent papers, including one in BMC Structural Biology , have revealed atomic structures of the enzymes that catalyze the synthesis of cGMP providing new clues about the molecular basis of substrate specificity and allosteric regulation in nucleotide cyclases. (biomedcentral.com)
  • PDE3 enzymes are involved in regulation of cardiac and vascular smooth muscle contractility. (wikipedia.org)
  • The zipper-closure role of the enzyme functions with divalent metal for inclusion of the cyclic nucleotide cAMP and cGMP in DNA. (novapublishers.com)
  • The promethazine effect on microvillus membrane phosphorylation was specific, since neither cAMP- and cGMP-induced phosphorylation in the microvillus membrane nor the stimulation by Ca 2+ -CaM of myosin light chain kinase phosphorylation of myosin light chain were affected by promethazine. (johnshopkins.edu)
  • The similar, and unusual sensitivity to low concentrations of promethazine on ileal microvillus membrane phosphorylation increased by Ca 2+ -CaM and on ileal electrolyte transport is consistent with Ca 2+ -CaM-dependent microvillus membrane phosphorylation being involved in the regulation of active electrolyte transport in ileal absorptive cells. (johnshopkins.edu)
  • Cohen, ME, Sharp, GWG & Donowitz, M 1986, ' Suggestion of a role for calmodulin and phosphorylation in regulation of rabbit ileal electrolyte transport: Effects of promethazine ', American Journal of Physiology - Gastrointestinal and Liver Physiology , vol. 251, no. 5, pp. 14/5. (johnshopkins.edu)
  • The PDEs belong to at least eleven related gene families, which are different in their primary structure, substrate affinity, responses to effectors, and regulation mechanism. (wikipedia.org)
  • Overall, this molecular mechanism could be used to propose a model linking environmental stimulus resulting in cAMP and the rate of gene expression. (novapublishers.com)
  • The greater activity of cAMP-Me2+-DNA complex with regard to a stabilized double helix allows for the introduction of a mechanism for genetic induction vs constitutive state. (novapublishers.com)
  • Für diese Domäne konnte auf struktureller Ebene eine Homologie zu zyklischen Nukleotid-Bindungsdomänen vorhergesagt und eine Bindung an cAMP und cGMP experimentell demonstriert werden. (uni-wuerzburg.de)
  • Methoden: Anhand von flussabhängigen isometrischen Tonusmessungen, glattmuskulären Potenzialableitungen und Bestimmung der zyklischen Nukleotide cAMP und cGMP in explantierten menschlichen Koronararterien (n=22 Transplantationspatienten) untersuchten wir eine Interaktion zwischen Adrenorezeptoren und der HDL- induzierten Vasorelaxation. (fu-berlin.de)
  • Not considering MB itself, blocking soluble guanylate cyclase (sGC), the final NO/cGMP messenger, in smooth muscle is underestimated and deserves a place in the present and future. (biomedcentral.com)
  • Figure 1 shows how the Ca 2+ /cAMP signaling interaction could be pharmacologically modulated by the combined use of the Ca 2+ channel blockers (CCB) and drugs that promote the increase of [cAMP] c (cAMP-enhancer compounds). (researchgate.net)
  • G-proteins agonists and NO/cGMP blockers: unexplored frontiers in the pharmaceutical industry. (biomedcentral.com)
  • ATP binding of Rv3651 in our screen further suggests nucleotide binding activity of Rv3651, in particular cAMP binding. (ssgcid.org)
  • There include the genes ecoding AC and PDE cAMP acceptors (CRP), which are transcription factors activated by this nucleotide and genes encoding proteins playing an important role in different physiological processes whose promoters have the CRP binding sequence. (am-online.org)
  • Our research interests are in the field of cyclic nucleotide signaling and cardiovascular biology, with a particular focus on cyclic nucleotide phosphodiesterases (PDEs) that catalyze the hydrolysis of cyclic nucleotide second messengers (cAMP and cGMP). (rochester.edu)
  • In sea urchin sperm, a cyclic nucleotide-gated K + channel (CNGK) mediates a cGMP-induced hyperpolarization that evokes Ca 2+ influx. (elifesciences.org)
  • Because cell behavior is a dynamic process influenced by numerous factors, we will attempt to emphasize how changes in the activity, expression, and targeting of PDE influence cyclic nucleotide-mediated regulation of the behavior of these cells. (aspetjournals.org)
  • We are especially interested in the interplay between cAMP and cGMP signalling and its role in heart pathophysiology. (ox.ac.uk)
  • As cAMP plays a key role in the regulation of excitation-contraction coupling in the heart, we want to understand how local cAMP signals affect cardiac physiology and we aim at establishing how disruption of local control of signal propagation leads to pathological conditions such as cardiac hypertrophy and heart failure. (ox.ac.uk)
  • Compartmentalized cAMP signalling and control of cardiac rhythm. (ox.ac.uk)
  • Regulation of cardiac function by cAMP nanodomains. (ox.ac.uk)
  • PDE3A and PDE3B have strikingly similar pharmacological and kinetic properties, but the distinction is in expression profiles and affinity for cGMP. (wikipedia.org)
  • The pharmacological modulation of Ca2+/cAMP signalling interaction is also cited. (researchgate.net)
  • We propose that lcn2 is an autocrine mediator of reactive astrocytosis based on the multiple roles of lcn2 in the regulation of cell death, morphology, and migration of astrocytes. (jneurosci.org)
  • GAF domains bind the secondary messengers cAMP and cGMP. (ssgcid.org)
  • The cyclic mononucleotides cAMP and cGMP are potent signaling molecules that exert profound effects on cellular homeostasis. (biomedcentral.com)
  • Their expression in vascular smooth muscle is altered under specific conditions such as elevated cAMP and hypoxia. (wikipedia.org)
  • With this „in cell" calibration approach we intend to directly correlate FRET signals to cAMP concentrations. (ox.ac.uk)
  • cAMP profoundly affects Mtb gene regulation and is required for virulence, and secretion of cAMP into the host disrupts the host's immune response to infection (Bai et al . (ssgcid.org)
  • Both substitutions affect highly conserved amino acids located in the regulatory GAF-B domain, which, by binding to cAMP, stimulates the activity of the PDE10A catalytic domain. (northwestern.edu)
  • The coordinated actions of these domains ensure fine tuned-regulations of the catalytic domain. (iisc.ac.in)
  • Inverse to the reported increase in sensitivity caused by NO shortage, concentrating NO attenuated the cGMP response in a concentration-dependent manner. (rupress.org)
  • They also participate in the regulation of the contraction of smooth muscles, including the smooth muscles of blood vessels. (selfgrowth.com)
  • In vitro functional studies showed that neither substitution affects the basal PDE10A activity, but they severely disrupt the stimulatory effect mediated by cAMP binding to the GAF-B domain. (northwestern.edu)
  • Diese Daten zeigen, dass Popdc1 eine wichtige Funktion bei der Regulation der Schrittmacheraktivität, der Aufrechterhaltung der Sinusknotenmorphologie und der Modulation von Ionenkanälen aufweist. (uni-wuerzburg.de)
  • cGMP (during follicular growth) can prevent untimely oocyte meiotic resumption up to ovulation (after LH surge, after increase in LH). (kiev.ua)
  • The cAMP-Me2+-DNA complex by increasing a turn-on activity could consolidate cAMP stimulus, allowing genetic variance by insertion of cAMP, by adhesion of cAMP to stimulate a similar area of the DNA at different stages on the overall evolutionary/adaptive response to environmental stress. (novapublishers.com)
  • Post-translational regulation of Rho activity has been shown specifically for RhoA. (phosphosolutions.com)