2002 3 5 cyclic amp phosphodiesterases. Medical search. Frequent questions

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)
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)
Bronchiolar obstruction, which causes airway obstruction in hyperresponsive airways, often results from the contraction of the airway's smooth muscles, increased viscid mucous secretions, and mucosal oedema consequent upon a reduced cyclic 3,5-adenosine monophosphate (c-AMP). (biomedcentral.com)
Tissue hypoxia, as occurs in sepsis, enhances breakdown of adenosine triphosphate (ATP) to adenosine monophosphate (AMP), which is then dephosphorylated by the cytosolic 5'nucloeotidase to adenosine [ 4 ]. (biomedcentral.com)
We used a step-down avoidance task to evaluate short-term memory and 3ʹ-5ʹ-cyclic adenosine monophosphate (cAMP) assay to detect cAMP levels. (einj.org)
They are highly specific for the hydrolysis of 3ʹ-5ʹ-cyclic adenosine monophosphate (cAMP), and are thus a key modulator of intracellular cAMP signaling pathways. (einj.org)
Oocyte arrest at the diplotene stage is maintained in part through the activity of phosphodiesterase enzymes that catalyze the hydrolysis of cyclic adenosine monophosphate (cAMP) into AMP [ 1 , 2 ]. (biomedcentral.com)

Chen, Z.S., Lee, K. and Kruh, G.D. (2001) Transport of Cyclic Nucleotides and Estradiol 17-Beta-d-glucuronide by Multidrug Resistance Protein 4. (scirp.org)
Bronchoconstriction, a state of bronchial smooth muscle tone is modulated by the interactions of the beta-adrenergic receptors and the metabolism of the intracellular cyclic nucleotides. (biomedcentral.com)
Cyclic nucleotides, like other nucleotides, are composed of three functional groups: a ribose sugar, a nitrogenous base, and a single phosphate group. (pancreapedia.org)
A cyclic nucleotide, unlike other nucleotides, has a cyclic bond arrangement between the ribose sugar and the phosphate group. (pancreapedia.org)
There are two main groups of cyclic nucleotides: the canonical or well-established and the non-canonical or unknown-function cyclic nucleotides. (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)
The non-canonical cyclic nucleotides include the purines inosine-3',5'-cyclic monophosphate (cyclic IMP), xanthosine-3',5'-cyclic monophosphate (cyclic XMP) and the pyrimidines cytidine-3',5'-cyclic monophosphate (cyclic cCMP), uridine-3',5'-cyclic monophosphate (cyclic UMP), and thymidine-3',5'-cyclic monophosphate (cTMP) (145). (pancreapedia.org)
An overview of the non-canonical cyclic nucleotides is provided in Section V. (pancreapedia.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)
This cyclic conformation allows cyclic nucleotides to bind to proteins to which other nucleotides cannot. (pancreapedia.org)
Dr. Beavo is being recognized for his research on the identification, regulation and functions of cyclic nucleotide phosphodiesterases, work on cyclic nucleotides, and for his strong commitment to mentoring. (aspet.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)
Considerably higher resistance against cyclic nucleotide phosphodiesterases compared to dibutyryl- or 8-Br-cAMP (Cat. (biolog.de)
In 1977, Dr. Beavo joined the department of pharmacology at the University of Washington, where his research revealed 11 diverse families of cyclic-nucleotide phosphodiesterases with different substrate specificity and regulation. (aspet.org)

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)

Selective phosphodiesterase (PDE) inhibitors improve the formation of hippocampus-dependent memories in several rodent models of cognition. (springer.com)
2005 ). cAMP and cGMP are hydrolyzed by phosphodiesterase (PDE) enzymes, and inhibitors of PDEs (PDE-Is) produce cognition-enhancing effects in animal models of cognition. (springer.com)
Phosphodiesterase inhibitors (PDIs) have important vascular and myocardial protective effects and thus have shown therapeutic usefulness in the clinical settings for treatment of patients with heart failure, pulmonary hypertension, and coronary artery disease. (biomedjournal.com)
The potential activity for selective phosphodiesterase inhibitors as therapeutic agents was predicted as early as 1977 by Weiss and Hait (Weiss and Hait, 1977). (biomedjournal.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)
Accordingly, over the last few years the use of PDE 5 inhibitors has been expanded to the therapeutic management of some cardiovascular disorders, including heart failure (HF). (ecrjournal.com)
Among all PDEs, PDE 5 , which is inhibited by sildenafil and other inhibitors of clinical use, has been widely investigated. (ecrjournal.com)
Sildenafil (Viagra), vardenafil (Levitra) and tadanafil (Cialis) are the three specific PDE 5 inhibitors in current clinical use, 5 which, despite similar although not identical mechanisms of action and structural similarity, present some significant differences regarding potency and selectivity. (ecrjournal.com)
Activation of A 2A ARs results in an increase in cyclic AMP concentration in inflammatory cells which is increased further by concurrent type IV phosphodiesterase inhibitors. (biomedcentral.com)

When cGMP (1000 μM) was added to the cell culture medium for 5 days the cell densities were reduced with 37% below baseline and cGMP in increased from 5.3 to 195 pmol/10 7 cells. (scirp.org)
A corresponding effect was observed after addition of 1000 μM cGMP and 1000 μM IBMX for 3 days. (scirp.org)
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)
Phosphodiesterases (PDEs) hydrolyze the phosphodiester bond of cAMP and cGMP to form the inactive 5′-AMP and 5′-GMP. (biomedjournal.com)
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)
On the horizon, novel insights into metabolism and energy homeostasis reveal guanosine 3′,5′-cyclic monophosphate (cGMP) signaling circuits as emerging targets for antiobesity pharmacotherapy. (eddoctor24h.com)

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)
A phosphodiesterase inhibitor is a drug that blocks one or more of the five subtypes of the enzyme phosphodiesterase (PDE) selectively in the brain. (biomedjournal.com)
We investigated the effects of pentoxifylline, a methylxanthine derivative and type-4 phosphodiesterase inhibitor, on short-term memory and apoptotic neuronal cell death in the hippocampus following perinatal hypoxic-ischemia in newborn rats. (einj.org)
Pentoxifylline is a methylxanthine derivative and type-4 phosphodiesterase (PDE-4) inhibitor. (einj.org)

In mammals, adenosine 3', 5'-cyclic monophosphate (cAMP) is known to play highly important roles in sperm motility and acrosomal exocytosis. (plos.org)
Cyclic AMP (adenosine 3', 5'-cyclic monophosphate) is an important player in sperm function. (plos.org)
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)

It catalyses the following reaction adenosine 3′,5′-cyclic phosphate + H2O ⇌ {\displaystyle \rightleftharpoons } AMP This enzyme requires Mg2+ or Mn2+ for activity. (wikipedia.org)
ATX (also known as ENPP2) is a 125 kDa-secreted enzyme from the family of ectonucleotide pyrophosphatases/phosphodiesterases (reviewed by [ 15 ]) located on Chr8q24 [ 16 ]. (hindawi.com)
The ability of the enzyme to use both O 2 and fumarate in cofactor reoxidation enables it to function under both aerobic and anaerobic conditions [5]. (enzyme-database.org)
The enzyme is a member of the succinate dehydrogenase/fumarate-reductase family of enzymes [5]. (enzyme-database.org)
A cyclase enzyme (lyase) catalyzes the formation of the cyclic nucleotide from its nucleotide triphosphate precursor ( Figure 1 ). (pancreapedia.org)

2001 Oct. 39(10):520-5. (medscape.com)
2001). The substrate specificities include the enzymes which are specific for cAMP hydrolysis, those for cyclic GMP hydrolysis (Mehats et al. (biomedjournal.com)

Enzymes that catalyze the hydrolysis of cyclic GMP to yield guanosine-5'-phosphate. (umassmed.edu)
2 The substrate specificities include enzymes that are specific for cyclic AMP hydrolysis, enzymes for cyclic GMP hydrolysis 3 and those that hydrolyse both. (ecrjournal.com)
The principal process by which intracellular cAMP levels are reduced is via hydrolysis by the phosphodiesterase enzymes. (biomedcentral.com)

J Exp Biol (2004) 207 (5): 743-748. (silverchair.com)

21. Johansson S & T ljedal I-B: Stimulation of 5-nucleotidase activity in the pancreatic islets by glucagon. (taljedal.se)

The production of estrogen and at a lower magnitude testosterone by the theca of the growing follicle increases 2 to 3 weeks before the production of the first egg and contributes to the development of reproductive organs and the synthesis of egg constituents [ 1 - 6 ]. (biomedcentral.com)

IBMX (3-isobutyl-1-methylxanthine), used as investigative tool in pharmacological research. (biomedjournal.com)
At Vanderbilt, Dr. Beavo discovered that methylxanthines, like IBMX, inhibit phosphodiesterases, laying the key groundwork for this pharmacology. (aspet.org)
Relative abundance of mature MIR21 was quantified at 0, 8, 16, 24, 32, and 42 h of in vitro (IVM) with or without treatment with 3-isobutyl-1-methylxanthine (IBMX). (biomedcentral.com)

Characterization of cyclic AMP phosphodiesterase isozymes in rat parotid gland. (shengsci.com)

2 Three PDE 5 isoforms have been described: PDE 5 A 1 , A 2 and A 3 . (ecrjournal.com)

In addition, may inhibit phosphodiesterase activity, leading to increased cyclic-3', 5'-AMP within platelets and formation of potent platelet activator thromboxane A2. (medscape.com)

Cyclic AMP (cAMP) plays a crucial role in neonatal airway function, tone, and caliber. (biomedcentral.com)

We show that W-7 acts on an acidic Ca 2+ -store: it abolished ATP-dependent vesicular acidification, inhibited V-type H + ATPase activity more potently than the weaker antagonist W-5 and caused vesicular Ca 2+ -leakage. (biomedcentral.com)

Elks, M. L. & Manganiello, V. C. Antilipolytic action of insulin: role of cAMP phosphodiesterase activation. (nature.com)
Risk factors for depression initiate an infection-like inflammation in the brain that involves activation microglial Toll-like receptors and glycogen synthase kinase-3β (GSK3β). (mdpi.com)
In ischemic animal models, caspase-3 activation is implicated in neuronal apoptosis [ 3 , 5 , 9 ]. (einj.org)
Clopidogrel exerts its antiplatelet effect by inhibiting the binding of adenosine diphosphate (ADP) to its receptor (P2Y12) and consequent ADP-mediated platelet activation [ 3 ]. (hindawi.com)
heat of Activation in the geranylgeranyl of autosomal rich complexes is on the result( interaction) and is circular recruiting of the 5' such mechanism( 5'-UTR) for an descending grove replication step. (evakoch.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)
The increased cAMP acting on submucosal glands influences water fluxes and hydration status across the airway epithelium with a reduction in the viscosity and tenacity of the secreted mucus [ 4 , 5 ]. (biomedcentral.com)
Concentration of cAMP in equine neutrophils induced by 5 adenosine A 2A receptor agonists (A) and effects of ZM241385 and MRS1706 on ATL313-induced accumulation of cAMP (B). Each point represents the mean ± SEM of 3 replicates. (avma.org)

Cyclic GMP was able to mimic the antiproliferative effect of SNP on HEK293 cells. (scirp.org)
Cyclic AMP also controls the clearance of the airway mucus by modulating the ciliary beat frequency [ 6 ] and suppresses the pro-inflammatory activities of the body's immune and inflammatory cells. (biomedcentral.com)
An increase in the number of TUNEL-positive cells is reflective of apoptotic cell death [ 3 , 6 , 8 ]. (einj.org)
Blood tests revealed severe leukopenia (white cells 1 × 10 3 / μ L) with marked neutropenia (neutrophils 3%), anaemia (haemoglobin 9.9 g/dL), and an important rise in inflammatory markers (C-reactive protein 122 mg/dL). (hindawi.com)
Higher cells of download Hanging Sam: A Military and mental Canadian initiation in the 5'-end novo depends the lipid protein directly than NALP1-mediated deafness to the chain. (evakoch.com)

The coxsackievirus and adenovirus receptor acts as the receptor for the 4 most common viruses that cause human myocarditis: type C (type 2 and type 5) adenovirus and coxsackievirus B3 and B4. (medscape.com)
Ca 2+ -influx is strongly reduced in the IplA minus strain that should lack an IP 3 receptor-like Ca 2+ -channel [ 30 ]. (biomedcentral.com)
Achondroplasia (ACH), the most common form of human dwarfism, is caused by an activating autosomal dominant mutation in the fibroblast growth factor receptor-3 gene. (bvsalud.org)

Nevertheless, inappropriate or excessive apoptosis is implicated in several neurological disorders [ 3 , 6 , 7 ]. (einj.org)

Cyclic nucleotide signaling can be initiated by two general mechanisms. (pancreapedia.org)

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

Neuronal apoptosis is closely associated with brain damage induced by ischemia/reperfusion injury [ 3 - 5 ]. (einj.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)

Cytosolic Ca 2+ is taken up into an IP 3 -sensitive Ca 2+ -store as well as into acidic Ca 2+ -stores [ 22 - 26 ]. (biomedcentral.com)

Calmodulin-dependent cyclic nucleotide phosphodiesterase in an experimental rat model of cardiac ischemia-reperfusion. (ouhsc.edu)

2022 Mar;298(3):101740. (leibniz-fmp.de)

The A 3 isoform is located in tissues having cardiac or smooth muscle constituents, such as the heart, bladder, prostate, urethra, penis, uterus and skeletal muscle. (ecrjournal.com)

If its negative charge is not reduced, the nucleotide triphosphate cannot be approached by a nucleophile, which is, in this reaction, the 3' hydroxyl group of the ribose (183). (pancreapedia.org)
The end products of this catalytic reaction are a cyclic nucleotide (cyclic AMP or cyclic GMP) and a pyrophosphate group. (pancreapedia.org)

9 Another cross-reactivity is that found with PDE 11 , which may be responsible for the development of back pain and myalgia as side effects of tadanafil due to the low selectivity of the compound for PDE 5 over PDE 11 . (ecrjournal.com)

Pharmacology & Pharmacy , 5 , 262-271. (scirp.org)

LPA receptors and autotaxin (ATX), a secreted phosphodiesterase that produces this phospholipid, are overexpressed in many cancers and impact several features of the disease, including cancer-related inflammation, development, and progression. (hindawi.com)
Adenosine can bind to four G protein coupled receptors, A 1 , A 2A , A 2B , and A 3 . (biomedcentral.com)

At least 1/3 of proteases and antiproteases identified in egg yolk and vitelline membrane proteomes are expressed similarly in the liver regardless of the maturity of hens, and have been initially identified as regulators of haemostasis and inflammatory events. (biomedcentral.com)

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)
Pilz, R.B. and Broderick, K.E. (2005) Role of Cyclic GMP in Gene Regulation. (scirp.org)
Caspase-3 is one of the most widely studied caspases, and plays a key-role in apoptosis. (einj.org)

Adenosine monophosphate8

Nucleotides11

Nucleotide phosphodiesterases3

Inhibition1

Inhibitors9

CGMP6

Inhibitor6

Monophosphate3

Enzyme5

20012

Hydrolysis3

Biol1

Stimulation1

Increases1

IBMX3

Characterization1

Isoforms1

Inhibit1

Plays a crucial role1

Activity1

Activation5

CAMP3

Cells5

Receptor3

Neurological1

Signaling1

Agonist1

Neuronal1

20161

Cytosolic1

Reperfusion1

20221

Cardiac1

Reaction2

Compound1

Pharmacology1

Receptors2

Inflammatory1

Role3