Intracellular cyclic nucleotide phosphodiesterases type 6. Medical search. Frequent questions

Cyclic di-AMP (also called c-di-AMP and c-di-adenosine monophosphate) is a second messenger used in signal transduction in bacteria and archaea. (wikipedia.org)
It is one of many ubiquitous nucleotide second messengers including cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), guanosine pentaphosphate ((p)ppGpp), and cyclic di-GMP (c-di-GMP). (wikipedia.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)
Activated olfactory receptors then activate intracellular G protein, guanine nucleotide-binding protein (GNAL), adenylate cyclase, and the production of cyclic adenosine monophosphate (cAMP). (psychologic.science)
Adenyl Cyclase - A membrane-bound enzyme that converts adenosine monophosphate to cyclic adenosine monophosphate (cAMP), an intracellular second messenger. (poisonfluoride.com)

c-di-AMP is a signaling nucleotide used in signaling pathways that trigger outputs by using receptor or target proteins to sense c-di-AMP concentrations in the cell. (wikipedia.org)
Since cyclic di-AMP is a signaling nucleotide, it is presumed to adhere to the same regulation pathways, where environmental changes are sensed by synthesis or degradation enzymes, which modulate enzyme concentration. (wikipedia.org)
At high concentrations, cyclic di-AMP binds to receptor and target proteins to control specific pathways. (wikipedia.org)
Zinc helps to enhance the interferon type 1 response to the virus and participates in many regulatory pathways. (frontiersin.org)
It plays a key role during sperm capacitation [ 3 - 6 ] and the acrosomal exocytosis [ 7 - 10 ], where it affects different intracellular signalling pathways. (plos.org)
We examined the role of cGMP-dependent signaling pathways and intracellular Ca(2+)stores in mediating the positive chronotropic effect of NO donors. (ox.ac.uk)
6. Mewe M., Bauer C.K., Müller D., Middendorff R. Regulation of spontaneous contractile activity in the bovine epididymal duct by cyclic guanosine 5'-monophosphate-dependent pathways. (abvpress.ru)
Our results indicate that context-dependent recruitment of alternative intracellular signaling pathways within a single sensory neuron type conveys opposite hedonic valences, thereby providing a robust mechanism for odorant encoding and discrimination at the periphery. (plos.org)

It is known to act through protein phosphorylation via PRKA and through the activation of guanine nucleotide exchange factors like EPAC. (plos.org)
There are two types of nitrogenous bases: purines (adenine and guanine) and pyrimidines (cytosine, uracil and thymine). (pancreapedia.org)
The two well-established cyclic nucleotides are adenosine-3',5'-cyclic monophosphate (cyclic AMP) and guanine-3',5'-cyclic monophosphate (cyclic GMP). (pancreapedia.org)
After a ligand binds to the GPCR, it activates a heterotrimeric G-protein, which is composed of three subunits: a guanine nucleotide binding α-subunit, and a βγ-heterodimer (98). (pancreapedia.org)

In lots of cells, the consequences of Simply no are mediated by era of guanosine 3,5 monophosphate (cGMP) [6]. (sipurpashut.net)
Cyclic guanosine monophosphate can be an intracellular regulator CHDI-390576 in both endocrine and non-endocrine systems [7]. (sipurpashut.net)
Cyclic guanosine monophosphate is usually a cyclic nucleotide the synthesis of which is usually catalyzed via guanylate cyclase, and CHDI-390576 numerous cyclic nucleotide phosphodiesterases (PDE) can degrade it. (sipurpashut.net)
Garg, U.C. and Hassid, A. (1989) Nitric Oxide-Generating Vasodilators and 8-Bromo-cyclic Guanosine Monophosphate Inhibit Mitogenesis and Proliferation of Cultured Rat Vascular Smooth Muscle Cells. (scirp.org)
Enzymes that catalyze the hydrolysis of cyclic GMP to yield guanosine-5'-phosphate. (umassmed.edu)

Role of cGMP-inhibited phosphodiesterase and sarcoplasmic calcium in mediating the increase in basal heart rate with nitric oxide donors. (ox.ac.uk)
Nitric oxide (NO) donors increase heart rate (HR) through a guanylyl cyclase-dependent stimulation of the pacemaker current I(f), without affecting basal I(Ca-L). The activity of I(f)is known to be enhanced by cyclic nucleotides and by an increase in cytosolic Ca(2+). (ox.ac.uk)
The signal source can be either extracellular, such as nitric oxide (NO) (114), or intracellular, such as bicarbonate (189). (pancreapedia.org)
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)

2. Benau D., Szabo E.I., Terner C. Endogenous inhibitors of cyclic adenosine 3',5'-monophosphate-phosphodiesterase in rat epididymis. (abvpress.ru)

Hormones mobilize intracellular second messengers and initiate signalling cascades involving protein kinases and phosphatases, which are often spatially compartmentalized by anchoring proteins to increase signalling specificity 1 . (nature.com)

The inhibitory effects of cAMP on sIL-6Ra/IL-6-stimulated phosphorylation of ERK1,2 and STAT3 were abolished by either short interfering (si) RNA-mediated knockdown or genetic ablation of suppressor of cytokine signalling-3 (SOCS-3). (gla.ac.uk)
Ser-473 phosphorylation is enhanced by interaction with AGAP2 isoform 2 (PIKE-A). Ser-473 phosphorylation is enhanced in focal cortical dysplasias with Taylor-type balloon cells. (stjohnslabs.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)

Examples include: antimalarial agents such as chloroquine and hydroxychloroquine, antivirals such as lopinavir/ritonavir and remdesivir, and tocilizumab as an anti-interleukin 6 (IL-6) receptor antibody ( 21 - 24 ). (frontiersin.org)
Here we demonstrate that elevation of cyclic AMP (cAMP) levels in human umbilical vein endothelial cells (HUVECs) specifically attenuates ERK1,2 activation in response to either leptin or a soluble interleukin IL-6 receptor-α/IL-6 (sIL-6R-α/IL-6) trans-signalling complex but not protein kinase C activator phorbol 12-myristate 13-acetate. (gla.ac.uk)
These olfactory receptors are a type of G protein-coupled receptor, which means the receptors are inherently metabotropic. (psychologic.science)
Each OSN singly expresses only one type of olfactory receptor, which is a phenomenon that has been called the "one neuron, one receptor" rule. (psychologic.science)
Each olfactory receptor cell states only one type of olfactoryreceptor (OR), but many separate olfactory receptor cells express ORs whichbind the same set of odors. (maryelizabethbodycare.com)
The axons of olfactory receptor cells which expressthe same OR converge to form glomeruli in the olfactory bulb.Function:ORs, which are positioned on the membranes of the cilia, have beencategorized as a complex type of ligand-gated metabotropic channels.Approximately 1000 different kind of genes code for olfactory receptor whichmake them larger gene family. (maryelizabethbodycare.com)

The inhibitory effect of cAMP could not be reversed by inhibition of cAMP-dependent protein kinase (PKA) but was blocked by depletion of the alternative intracellular cAMP sensor exchange protein activated by cAMP 1 (Epac1), which is also required to observe SOCS-3 accumulation in response to cAMP. (gla.ac.uk)

This cyclic conformation allows cyclic nucleotides to bind to proteins to which other nucleotides cannot. (pancreapedia.org)

Phosphodiesterase (PDE) enzymes degrade cyclic di-AMP to the linear molecule 5'-pApA (phosphadenylyl adenosine). (wikipedia.org)
In some bacteria, loss of the phosphodiesterases that degrade c-di-AMP leads to cell death. (wikipedia.org)
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)

It is hypothesized that cAMP signaling in the Golgi area and the cytosol in neurons is controlled through alteration of subcellular localization of PDE10A brought by activation of PKA in response to intracellular elevations of cAMP. (johnshopkins.edu)

The activated OR as a result activatesthe intracellular G-protein, GOLF (GNAL), adenylate cyclase and production ofcyclic AMP (cAMP) opens ion channels in the cell membrane, resulting in aninflux of sodium and calcium ions into the cell, and an efflux of chlorideions. (maryelizabethbodycare.com)

Cyclic di-AMP is synthesized by a membrane-bound diadenylate cyclase (also called diadenylyl cyclase, CdA, and DAC) enzyme called CdaA (DacA). (wikipedia.org)
GImM is the phosphoglucosamine mutase enzyme that interconverts glucosamine-6-phosphate to glucosamine-1-phosphate to later form cell wall peptidoglycan and other polymers. (wikipedia.org)
A cyclase enzyme (lyase) catalyzes the formation of the cyclic nucleotide from its nucleotide triphosphate precursor ( Figure 1 ). (pancreapedia.org)

Considerably higher resistance against cyclic nucleotide phosphodiesterases compared to dibutyryl or 8-Br-cAMP, no metabolic side effects. (biolog.de)

Synthesis is regulated a number of ways, including negative feedback inhibition and upregulation through a decrease in phosphodiesterase. (wikipedia.org)
Cyclic di-AMP has also been linked to bacterial RNA synthesis inhibition. (wikipedia.org)
Woolson, H. D. , Thomson, V. S. , Rutherford, C. , Yarwood, S. J. and Palmer, T. M. (2009) Selective inhibition of cytokine-activated extracellular signal-regulated kinase by cyclic amp via Epac1-dependent induction of suppressor of cytokine signalling-3. (gla.ac.uk)
Interestingly, the ability of cAMP elevation to inhibit IL-6 signalling was blocked by ERK inhibition. (gla.ac.uk)
It has been documented that PDE5 degrades 3C5-cGMP and its inhibition prospects to an increase in intracellular cGMP levels and subsequent activation of protein kinase G, resulting in a decrease in Ca2+ influx and consequent relaxation of smooth muscle tissue [11]. (sipurpashut.net)

The interaction with the non-selective PDE (cyclic nucleotide phosphodiesterase) inhibitor 3-isobutyl-1-methylxanthine (IBMX) was tested after three days. (scirp.org)
Zhang L, Zhang Z, Zhang RL, Cui Y, LaPointe MC, Silver B, Chopp M. Tadalafil, a long-acting type 5 phosphodiesterase isoenzyme inhibitor, improves neurological functional recovery in a rat model of embolic stroke. (umassmed.edu)
Phosphodiesterase inhibitor-mediated potentiation of adenovirus delivery to myocardium. (umassmed.edu)

We followed up this analysis by showing that loss of cln5 alters the intracellular and extracellular amounts of proliferation repressors during growth and increases the extracellular amount of conditioned medium factor, which regulates cAMP signalling during the early stages of development. (frontiersin.org)
Additionally, cln5 - cells displayed increased intracellular and extracellular amounts of discoidin, which is involved in cell-substrate adhesion and migration. (frontiersin.org)

Stimulation of soluble guanylyl cyclase (sGC) gives a rapid elevation of intracellular cGMP levels and relaxation of VSMC. (scirp.org)

Cyclic di-AMP synthesis is inhibited by the GImM I154F mutation in the lactococcus lactis bacterium. (wikipedia.org)
Cyclic di-AMP has been linked to fatty acid synthesis regulation in Mycobacterium smegmatis, the growth of S. aureus in conditions of low potassium, the sensing of DNA integrity in B. subtilis, and cell wall homeostasis in multiple species. (wikipedia.org)

During the depolarization event, when cAMP binds to the cyclic nucleotide-gated (CNG) ion channels, sodium and calcium diffuse into the cell. (psychologic.science)

In bacteria, cyclic di-AMP has been implicated in the control of growth, cell wall homeostasis, bacterial biofilm formation and virulence gene expression, heat and osmotic stress regulation and responses, sporulation, potassium transport, lysis, and antibiotic resistance. (wikipedia.org)
Differences in mortality due to COVID-19 infection may be explained to some degree by−174 IL-6 gene polymorphism. (frontiersin.org)
Although a high level of PDE10A gene expression is observed in the testis, information on the identity of the isoforms or on the cell type that express the PDE10 protein is lacking. (plos.org)
Pilz, R.B. and Broderick, K.E. (2005) Role of Cyclic GMP in Gene Regulation. (scirp.org)

Here, we detected altered intracellular activities of various carbohydrate enzymes and cathepsins during cln5 - growth and starvation. (frontiersin.org)

Cyclic nucleotides form when the phosphate group of the molecule of nucleotide triphosphate (ATP or GTP) is attacked by the 3' hydroxyl group of the ribose, forming a cyclic 3',5'-phosphate ester with release of pyrophosphate. (pancreapedia.org)
The overall resultof this negative feedback is that it stops the neuron from further activationwhen a new molecule of new odor came into the systemNumber of distinguishable odors:According to the scientific research humans can detect about more thanone trillion vast types of odors. (maryelizabethbodycare.com)

CaMKII will reduce cAMP levels by both deactivating adenyl cyclase and by activating phosphodiesterase, which hydrolyzes cAMP (Wei et al. (psychologic.science)
In the system, when other nucleotides are present, fluoride will - just like TSH - activate adenyl cyclase at low concentrations, while inhibiting same at higher concentrations. (poisonfluoride.com)

The I154F mutation inhibits CdA activity by binding to it more strongly than wild-type GImM binds. (wikipedia.org)
The nucleotide either binds to the helicase DDX41, which in turn activates the STING pathway, or directly binds to the STING protein. (wikipedia.org)

PLoS Biol 20(6): e3001677. (plos.org)

It is possible that in addition to enzymatic regulation, intracellular c-di-AMP levels can be regulated by active transport via multidrug resistance transporters that secrete c-di-AMP from the cytoplasm. (wikipedia.org)
Low levels of zinc have been associated with higher IL-6 responses. (frontiersin.org)
Plasma zinc levels are therefore only around 1 μg/ml, equal to 0.1% of total body zinc, but are still the most important reservoir for zinc homeostasis, which requires "free" or "labile" zinc mobilization ( 6 , 7 ). (frontiersin.org)

6-hour sleep deprivation reduced the light response in the SCN. (adxs.org)

As a sub-objective, since PDE10A transcript variants were reported strictly through analyses of bovine genomic sequence, we also wanted to determine the nucleotide and amino acid sequences by experimental evidence. (plos.org)
Goupil S, Maréchal L, El Hajj H, Tremblay M-È, Richard FJ, Leclerc P (2016) Identification and Localization of the Cyclic Nucleotide Phosphodiesterase 10A in Bovine Testis and Mature Spermatozoa. (plos.org)

Activator of protein kinase A (cyclic AMP agonist). (biolog.de)

7. Swinnen J.V., Joseph D.R., Conti M. Molecular cloning of rat homologues of the Drosophila melanogaster dunce cAMP phosphodiesterase: evidence for a family of genes. (abvpress.ru)

Cyclic nucleotides, like other nucleotides, are composed of three functional groups: a ribose sugar, a nitrogenous base, and a single phosphate group. (pancreapedia.org)

protein_coding" "AAC74850","yeaD","Escherichia coli","D-hexose-6-phosphate epimerase-like protein [Ensembl]. (ntu.edu.sg)

In eukaryotic cells, c-di-AMP is sensed and subsequently elicits a type I interferon (IFN) response, leading to the activation of defense mechanisms against viral infection. (wikipedia.org)
Cyclic di-AMP has been identified (along with 2'3'-cGAMP) as a ligand that induces closing of the STING dimer, leading to STING polymerization and pathway activation. (wikipedia.org)
Elks, M. L. & Manganiello, V. C. Antilipolytic action of insulin: role of cAMP phosphodiesterase activation. (nature.com)

Montelukast was found to attenuate both peripheral and central inflammation, reducing the expression of pro-inflammatory molecules (IL-1β, IL-6, TNF) in the brain. (biomedcentral.com)

The varied neuropathology, collectively termed encephalopathy of prematurity (EoP), includes grey and white matter injury and increases the incidence of a range of cognitive and motor deficits in later life [ 6 ], for which limited treatments are currently available. (biomedcentral.com)

IL-6 plays an important role in severe lung injury due to COVID-19 infection. (frontiersin.org)
The cone-enriched apoptotic protease caspase-7 ( Casp7 ) is thought to be triggered by endoplasmic reticulum (ER) stress and plays a pivotal role in mice deficient in the cone cyclic nucleotide-gated channels, a deficiency that causes achromatopsia in humans and in mice with autosomal dominant rhodopsin mutations, in particular the T17M mutation. (molvis.org)

In humans, cyclic di-AMP has been implicated in the control of innate immune response and antiviral response against pathogens. (wikipedia.org)
Our previous studies have suggested that two phosphodiesterase type 10A (PDE10A) variants, PDE10A1 and PDE10A2 transcripts, are mainly expressed in humans and that PDE10A2 and PDE10A3 transcripts are major variants in rats. (johnshopkins.edu)

The valence of individual chemicals is largely determined by the responding sensory neuron type, such that distinct subsets of chemosensory neurons drive either attraction or avoidance to different chemicals [ 25 , 26 ]. (plos.org)

Evidence for androgen-dependent phosphodiesterase activity in rat seminal vesicle and epididymis. (abvpress.ru)
However, when intact platelets were incubated with NO and then lysed, enhanced activity of phosphodiesterase type 5 was detected in the cytosol. (rupress.org)

[6] caffeine paralyzes and kills certain insects feeding upon the plant. (wikidoc.org)

Cyclic GMP was able to mimic the antiproliferative effect of SNP on HEK293 cells. (scirp.org)
17␤-Estradiol reduced the intracellular free cells. (drugstodaypdf.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)

This graph shows the total number of publications written about "3',5'-Cyclic-GMP Phosphodiesterases" by people in this website by year, and whether "3',5'-Cyclic-GMP Phosphodiesterases" was a major or minor topic of these publications. (umassmed.edu)

Interestingly, recombinant protein of wild-type PDE10A2, but not PDE10A2 mutant with an Ala replacement at Thr 16 , was distributed to cytosolic fractions by co-transfection with a plasmid encoding the catalytic subunit of PKA. (johnshopkins.edu)

Organisms1

Chemicals and Drugs48

Analytical, Diagnostic and Therapeutic Techniques and Equipment1

Phenomena and Processes12

Information Science3

Adenosine monophosphate5

Pathways8

Guanine4

Guanosine5

Nitric Oxide4

Inhibitors1

Protein Kinases1

Phosphorylation4

Receptor6

Alternative intracellular1

Proteins1

Degrade3

Subcellular Localization1

Adenylate cyclase1

Enzyme3

Dibutyryl1

Inhibition5

Inhibitor3

Extracellular2

Soluble1

Synthesis2

Calcium1

Gene4

Enzymes1

Molecule2

Adenyl cyclase2

Binds2

Biol1

Levels3

Deprivation1

Bovine2

Kinase1

Genes1

Functional1

Escherichia1

Activation3

Molecules1

Increases1

Role2

Humans2

Chemicals1

Activity2

Caffeine1

Cells2

Response1

Minor1

Interestingly1