A CALCIUM and CALMODULIN-dependent cyclic nucleotide phosphodiesterase subfamily. The three members of this family are referred to as type 1A, type 1B, and type 1C and are each product of a distinct gene. In addition, multiple enzyme variants of each subtype can be produced due to multiple alternative mRNA splicing. Although the type 1 enzymes are classified as 3',5'-cyclic-AMP phosphodiesterases (EC 3.1.4.17), some members of this class have additional specificity for CYCLIC GMP.
Enzymes that catalyze the hydrolysis of CYCLIC AMP to form adenosine 5'-phosphate. The enzymes are widely distributed in animal tissue and control the level of intracellular cyclic AMP. Many specific enzymes classified under this heading demonstrate additional spcificity for 3',5'-cyclic IMP and CYCLIC GMP.
A cyclic nucleotide phosphodiesterase subfamily that is found predominantly in inflammatory cells and may play a role in the regulation of CELL-MEDIATED IMMUNITY. The enzyme family includes over twenty different variants that occur due to multiple ALTERNATIVE SPLICING of the mRNA of at least four different genes.
A cyclic nucleotide phosphodiesterase subfamily that is inhibited by the binding of CYCLIC GMP to an allosteric domain found on the enzyme and through phosphorylation by regulatory kinases such as PROTEIN KINASE A and PROTEIN KINASE B. The two members of this family are referred to as type 3A, and type 3B, and are each product of a distinct gene. In addition multiple enzyme variants of each subtype can be produced due to multiple alternative mRNA splicing.
A cyclic nucleotide phosphodiesterase subfamily that is activated by the binding of CYCLIC GMP to an allosteric domain found on the enzyme. Multiple enzyme variants of this subtype can be produced due to multiple alternative mRNA splicing. The subfamily is expressed in a broad variety of tissues and may play a role in mediating cross-talk between CYCLIC GMP and CYCLIC CMP pathways. Although the type 2 enzymes are classified as 3',5'-cyclic-AMP phosphodiesterases (EC 3.1.4.17), members of this class have additional specificity for CYCLIC GMP.
A class of enzymes that catalyze the hydrolysis of one of the two ester bonds in a phosphodiester compound. EC 3.1.4.
Nucleoside-2',3'-cyclic phosphate nucleotidohydrolase. Enzymes that catalyze the hydrolysis of the 2'- or 3'- phosphate bonds of 2',3'-cyclic nucleotides. Also hydrolyzes nucleoside monophosphates. Includes EC 3.1.4.16 and EC 3.1.4.37. EC 3.1.4.-.
Cyclic nucleotides are closed-chain molecules formed from nucleotides (ATP or GTP) through the action of enzymes called cyclases, functioning as second messengers in various cellular signaling pathways, with cAMP and cGMP being the most prominent members.
Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases.
Enzymes that catalyze the hydrolysis of cyclic GMP to yield guanosine-5'-phosphate.
A cyclic nucleotide phosphodiesterase subfamily that is highly specific for CYCLIC GMP. It is found predominantly in vascular tissue and plays an important role in regulating VASCULAR SMOOTH MUSCLE contraction.
Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)
A cyclic nucleotide phosphodiesterase subfamily that is highly specific for CYCLIC AMP. Several isoforms of the enzyme type exist, each with its own tissue localization. The isoforms are encoded by at least two genes and are a product of multiple alternative splicing of their mRNAs.
An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.
A phosphodiesterase 4 inhibitor with antidepressant properties.
A potent cyclic nucleotide phosphodiesterase inhibitor; due to this action, the compound increases cyclic AMP and cyclic GMP in tissue and thereby activates CYCLIC NUCLEOTIDE-REGULATED PROTEIN KINASES
'Purines' is a term used in medical biochemistry to refer to naturally occurring heterocyclic aromatic organic compounds, which include adenine and guanine (components of nucleotides and nucleic acids), and are formed in the body from purine bases through various metabolic processes.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
The rate dynamics in chemical or physical systems.
A cyclic nucleotide phosphodiesterase subfamily that is highly specific for CYCLIC GMP. It is found predominantly in the outer segment PHOTORECEPTOR CELLS of the RETINA. It is comprised of two catalytic subunits, referred to as alpha and beta, that form a dimer. In addition two regulatory subunits, referred to as gamma and delta, modulate the activity and localization of the enzyme.
The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed)
Compounds that specifically inhibit PHOSPHODIESTERASE 3.
Compounds that specifically inhibit PHOSPHODIESTERASE 4.
Inhibitor of phosphodiesterases.
N-(1-Oxobutyl)-cyclic 3',5'-(hydrogen phosphate)-2'-butanoate guanosine. A derivative of cyclic GMP. It has a higher resistance to extracellular and intracellular phosphodiesterase than cyclic GMP.
A methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Theophylline inhibits the 3',5'-CYCLIC NUCLEOTIDE PHOSPHODIESTERASE that degrades CYCLIC AMP thus potentiates the actions of agents that act through ADENYLYL CYCLASES and cyclic AMP.
A phosphoric diester hydrolase that removes 5'-nucleotides from the 3'-hydroxy termini of 3'-hydroxy-terminated OLIGONUCLEOTIDES. It has low activity towards POLYNUCLEOTIDES and the presence of 3'-phosphate terminus on the substrate may inhibit hydrolysis.
A subgroup of cyclic nucleotide-regulated ION CHANNELS within the superfamily of pore-loop cation channels. They are expressed in OLFACTORY NERVE cilia and in PHOTORECEPTOR CELLS and some PLANTS.
Enzymes that catalyze the cleavage of a phosphorus-oxygen bond by means other than hydrolysis or oxidation. EC 4.6.
A positive inotropic cardiotonic agent with vasodilator properties. It inhibits cAMP phosphodiesterase type 3 activity in myocardium and vascular smooth muscle. Milrinone is a derivative of amrinone and has 20-30 times the inotropic potency of amrinone.
A cyclic nucleotide derivative that mimics the action of endogenous CYCLIC AMP and is capable of permeating the cell membrane. It has vasodilator properties and is used as a cardiac stimulant. (From Merck Index, 11th ed)
A group of compounds that are derivatives of oxo-pyrrolidines. A member of this group is 2-oxo pyrrolidine, which is an intermediate in the manufacture of polyvinylpyrrolidone. (From Merck Index, 11th ed)
Adenine nucleotides are molecules that consist of an adenine base attached to a ribose sugar and one, two, or three phosphate groups, including adenosine monophosphate (AMP), adenosine diphosphate (ADP), and adenosine triphosphate (ATP), which play crucial roles in energy transfer and signaling processes within cells.
A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.
A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.
An enzyme of the lyase class that catalyzes the formation of CYCLIC AMP and pyrophosphate from ATP. EC 4.6.1.1.
Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system.
An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. It is a direct-acting smooth muscle relaxant used in the treatment of impotence and as a vasodilator, especially for cerebral vasodilation. The mechanism of its pharmacological actions is not clear, but it apparently can inhibit phosphodiesterases and it may have direct actions on calcium channels.
Inosine cyclic 3',5'-(hydrogen phosphate). An inosine nucleotide which acts as a mild inhibitor of the hydrolysis of cyclic AMP and cyclic GMP and as an inhibitor of cat heart cyclic AMP phosphodiesterase.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.
An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.
Compounds that specifically inhibit PHOSPHODIESTERASE 5.
A long-acting derivative of cyclic AMP. It is an activator of cyclic AMP-dependent protein kinase, but resistant to degradation by cyclic AMP phosphodiesterase.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
Guanine nucleotides are cyclic or linear molecules that consist of a guanine base, a pentose sugar (ribose in the cyclic form, deoxyribose in the linear form), and one or more phosphate groups, playing crucial roles in signal transduction, protein synthesis, and regulation of enzymatic activities.
Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.
The process of cleaving a chemical compound by the addition of a molecule of water.
Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.
Purine bases found in body tissues and fluids and in some plants.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A group of indole-indoline dimers which are ALKALOIDS obtained from the VINCA genus of plants. They inhibit polymerization of TUBULIN into MICROTUBULES thus blocking spindle formation and arresting cells in METAPHASE. They are some of the most useful ANTINEOPLASTIC AGENTS.
'Cyclic P-Oxides' is a term used in medicinal chemistry to describe a class of organic compounds where a cyclic structure contains at least one peroxide bond (-O-O-), characterized by their unique chemical properties and potential therapeutic applications, particularly as anti-cancer or antiviral agents.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.

Potency and mechanism of action of E4021, a type 5 phosphodiesterase isozyme-selective inhibitor, on the photoreceptor phosphodiesterase depend on the state of activation of the enzyme. (1/318)

The ability of inhibitors selective for the type 5 phosphodiesterase isozyme (PDE5) to act on the photoreceptor PDE isozyme (PDE6, the central effector enzyme for visual transduction) is poorly understood. Because PDE5 inhibitors are currently used as therapeutic agents, it is important to assess the potency and mechanism of action of this class of PDE inhibitor on PDE6. We show that E4021 (sodium 1-[6-chloro-4-(3, 4-methylenedioxybenzyl)-aminoquinazolin-2-yl]piperidine-4-ca rboxylate sesquihydrate) inhibits activated PDE6 (KI = 1.7 nM) as potently as PDE5. This makes E4021 the most potent inhibitor of PDE6 discovered to date. The effectiveness of E4021 to inhibit nonactivated PDE6 (with bound inhibitory gamma subunits) is reduced 40-fold compared with the activated enzyme. Furthermore, at intermediate E4021 concentrations and high cGMP concentrations, nonactivated PDE undergoes activation of cGMP hydrolysis rather than inhibition. We demonstrate direct competition of E4021 and the gamma subunits for binding to the catalytic site. Measurements of cGMP binding to noncatalytic regulatory sites on the catalytic subunits of PDE6 rule out an allosteric effect of E4021 by direct binding to these noncatalytic sites. We conclude that E4021 is a competitive inhibitor of cGMP hydrolysis and that the gamma subunit also competes with both E4021 and substrate for catalytic site binding. An understanding of the effects of PDE5-targeted drugs on retinal PDE6 requires a knowledge of the complex interactions among substrate, drug, and inhibitory gamma subunit at the catalytic site of both nonactivated and activated forms of PDE6.  (+info)

cAMP-dependent induction of PDE5 expression in murine neuroblastoma cell differentiation. (2/318)

The present study demonstrates, in both hybrid NG108-15 and mouse neuroblastoma N18TG2 cells, the presence and regulation of PDE5 mRNA during cell differentiation. PDE5 cDNA probes in Northern blot analysis recognize a approximately 9 kb transcript in bovine lung as well as in mouse neuroblastoma cells. Hybridization on total RNA extracted from dibutyryl-cAMP-treated NG108-15 cells shows a 5-fold increase of PDE5 9 kb mRNA: such an increase is not observed in N18TG2 although we observed a similar increase in the enzymatic activity of both cell lines. Our data demonstrate that PDE5 gene expression can be regulated by cAMP and suggest the existence of a complex regulatory system for PDE5 activity.  (+info)

Inhibition of cyclic GMP-binding cyclic GMP-specific phosphodiesterase (Type 5) by sildenafil and related compounds. (3/318)

The cGMP-binding cGMP-specific phosphodiesterase (PDE5) degrades cGMP and regulates the intracellular level of cGMP in many tissues, including the smooth muscle of the corpus cavernosum of the penis. Sildenafil (Viagra), a specific PDE5 inhibitor, promotes penile erection by blocking the activity of PDE5, which causes cGMP to accumulate in the corpus cavernosum. In the present study, sildenafil, like other PDE5 inhibitors, stimulates cGMP binding to the allosteric sites of PDE5 by interacting at the catalytic site of this enzyme, but the drug does not compete with cGMP for binding at the allosteric sites. Both sildenafil and zaprinast are competitive inhibitors of PDE5, and double-inhibition analysis shows that these two inhibitors added together interact with the catalytic site of PDE5 in a mutually exclusive manner. After site-directed mutagenesis of each of 23 conserved amino acid residues in the catalytic domain of PDE5, the pattern of changes in the IC50 values for sildenafil or UK-122764 is similar to that found for zaprinast. However, among the three inhibitors, sildenafil exhibits the most similar pattern of changes in the IC50 to that found for the affinity of cGMP, implying similar interactions with the catalytic domain. This may explain in part the stronger inhibitory potency of sildenafil for wild-type PDE5 compared with the other inhibitors [sildenafil (Ki = 1 nM) > UK-122764 (Ki = 5 nM) > zaprinast (Ki = 130 nM)]. The affinity of each of these inhibitors for PDE5 is much higher than that of cGMP itself (Km = 2000 nM). It is concluded that residues such as Tyr602, His607, His643, and Asp754 may form important interactions for sildenafil in PDE5, but because these amino acids are conserved in all mammalian PDEs, the selectivity and potency of sildenafil is likely to be provided by a nonconserved residue or residues in the PDE5 catalytic domain.  (+info)

Improvement of mortality by long-term E4010 treatment in monocrotaline-induced pulmonary hypertensive rats. (4/318)

We investigated the effects of long-term treatment with a selective phosphodiesterase 5 inhibitor E4010, 4-(3-chloro-4methoxybenzyl)amino-1-(4-hydroxypiperidino)-6-phth alazin ecarbonitrile monohydrochloride, on the survival rate of rats with pulmonary hypertension induced by monocrotaline (MCT). After an s.c. injection of 40 mg/kg MCT (day 0), male Wistar rats of 4 weeks of age were divided into four groups. Vehicle-treated rats (control, n = 8) and MCT-treated rats (n = 32) were fed a commercial diet. E4010-treated rats were given a commercial diet containing 0.01% (E4010 0.01%, n = 32) and 0.1% (E4010 0.1%, n = 32) of E4010, respectively. At day 23, all rats in the control group and 28.1% of those in the MCT group (P <.01 versus control) were alive. Although the survival rate of E4010 0.01%-treated rats was not improved (50%) compared with MCT, those at 0.1% showed a significant difference (84. 4%, P <.01 versus MCT). For MCT rats (n = 9), right ventricle weight and the levels of plasma atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), cGMP, and cyclic AMP were higher compared with control (n = 8). In E4010 0.1%-treated rats (n = 27), the right ventricular hypertrophy was suppressed, and the increase in plasma cGMP level was amplified compared with MCT without any effects on plasma ANP, BNP, and cyclic AMP levels. Accordingly, we consider that the mechanism of action of E4010 may be related to the decreased pulmonary arterial pressure caused by the augmentation of pulmonary arterial relaxation through an ANP and/or BNP-cGMP system. These results suggest that E4010 will be useful for the treatment of pulmonary hypertension.  (+info)

Genomic origin and transcriptional regulation of two variants of cGMP-binding cGMP-specific phosphodiesterases. (5/318)

We have reported alternative splice variants of cGMP-binding cGMP-specific phosphodiesterases (PDE5A), i.e. rat PDE5A2, human PDE5A1, canine PDE5A1 and PDE5A2, which possess distinct N-terminal sequences. In this study, the DNA sequences corresponding to the unique N-terminal portions of PDE5A1 and PDE5A2 were shown to be tandemly located upstream of exons encoding the common region of PDE5A in both human and rat PDE5A genes. The presence of human PDE5A2 and rat PDE5A1 transcripts in lung was confirmed by reverse transcriptase-PCR. These results indicated that two variant forms of PDE5A exist in humans, canines and rats. We examined the tissue distribution of the two variants of human PDE5A in adult and fetal humans. The patterns of expression of the two alternatively spliced transcripts of human PDE5A in human tissues differed. Many putative regulatory elements including cAMP response elements were observed in the 5'-untranslated region and intron of the PDE5A gene. The levels of the PDE5A transcripts, especially the PDE5A2 transcripts, were increased by a cAMP analogue in cultured rat vascular smooth muscle cells, indicating that the PDE5A2 is an inducible variant of PDE5A in rats.  (+info)

Studies of the molecular mechanism of discrimination between cGMP and cAMP in the allosteric sites of the cGMP-binding cGMP-specific phosphodiesterase (PDE5). (6/318)

The regulatory domain of the cGMP-binding cGMP-specific 3':5'-cyclic nucleotide phosphodiesterase (PDE5) contains two homologous segments of amino acid sequence that encode allosteric cyclic nucleotide-binding sites, referred to as site a and site b, which are highly selective for cGMP over cAMP. The possibility that the state of protonation in these sites contributes to cyclic nucleotide selectivity was investigated. The binding of cGMP or cAMP was determined using saturation and competition kinetics at pH values between 5.2 and 9.5. The total cGMP binding by PDE5 was unchanged by variation in pH, but the relative affinity for cGMP versus cAMP progressively decreased as the pH was lowered. Using site-directed mutagenesis, a conserved residue, Asp-289, in site a of PDE5 has been identified as being important for cyclic nucleotide discrimination in this site. It is proposed that deprotonation of Asp-289 enhances the number and strength of bonds formed with cGMP, while concomitantly decreasing the interactions with cAMP.  (+info)

Autoregulation of nitric oxide-soluble guanylate cyclase-cyclic GMP signalling in mouse thoracic aorta. (7/318)

1. The sensitivity of the soluble guanylate cyclase (sGC)-cyclic guanosine-3',5'-monophosphate (cyclic GMP) system to nitric oxide (NO) was investigated in mouse aorta from wild type (WT) and NO synthase (NOS) knockout (KO) animals. 2. The NO donor, spermine-NONOate (SPER-NO) was more potent in aortas from eNOS KO mice compared to WT (pEC50 7.30+/-0.06 and 6.56+/-0.04, respectively; n=6; P<0.05). In contrast, the non-NO based sGC activator, YC-1 was equipotent in vessels from eNOS WT and KO mice. The sensitivity of aortas from nNOS and iNOS KO animals to SPER-NO was unchanged. Forskolin (an adenylate cyclase activator), was equipotent in vessels from eNOS WT and KO animals. 3. The cyclic GMP analogue, 8-Br-cGMP was equipotent in eNOS WT and KO mice (pEC50 4. 38+/-0.04 and 4.40+/-0.05, respectively; n=5; P>0.05). Zaprinast (10-5 M) a phosphodiesterase type V (PDE V) inhibitor, had no effect on the response to SPER-NO in vessels from eNOS WT or KO mice. 4. The NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 3x10-4 M) increased the potency of SPER-NO in aortas from WT mice (pEC50 6. 64+/-0.02 and 7.37+/-0.02 in the absence and presence of L-NAME, respectively; n=4; P<0.05). 5. In summary, there is increased sensitivity of vessels from eNOS KO animals to NO. Cyclic AMP-mediated dilatation is unchanged, consistent with a specific up-regulation of sGC - cyclic GMP signalling. The functional activity of cyclic GMP-dependent protein kinase (G-kinase) and PDE V was also unchanged, suggesting that sGC is the site of up-regulation. These alterations in the sensitivity of the sGC - cyclic GMP pathway might represent a mechanism for the dynamic regulation of NO bioactivity.  (+info)

Impaired cerebral vasodilator responses to NO and PDE V inhibition after subarachnoid hemorrhage. (8/318)

Subarachnoid hemorrhage (SAH) is associated with impaired nitric oxide (NO)-mediated cerebral vasodilatation. We tested the hypothesis that SAH causes alterations in the production of, hydrolysis of, or responsiveness to cGMP in the rat basilar artery in vivo. Rats were injected with saline or autologous blood into the cisterna magna. Two days later, effects of vasoactive drugs on basilar artery diameter were examined using a cranial window preparation. Vasodilator responses to ACh, sodium nitroprusside (SNP), and low concentrations (+info)

Cyclic nucleotide phosphodiesterases (PDEs) are a family of enzymes that regulate intracellular levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which are important second messengers involved in various cellular processes.

Type 1 PDEs (PDE1A, PDE1B, PDE1C) are calcium/calmodulin-regulated enzymes that hydrolyze both cAMP and cGMP with similar catalytic efficiency. They play a crucial role in the regulation of vascular smooth muscle contraction, platelet aggregation, and neuronal excitability.

Dysregulation of PDE1 activity has been implicated in various pathological conditions, including hypertension, cardiovascular diseases, and neurological disorders. Therefore, PDE1 inhibitors have emerged as potential therapeutic agents for the treatment of these conditions.

3',5'-Cyclic-AMP (cyclic adenosine monophosphate) phosphodiesterases are a group of enzymes that catalyze the breakdown of cyclic AMP to 5'-AMP. These enzymes play a crucial role in regulating the levels of intracellular second messengers, such as cyclic AMP, which are involved in various cellular signaling pathways.

There are several subtypes of phosphodiesterases (PDEs) that specifically target cyclic AMP, including PDE1, PDE2, PDE3, PDE4, PDE7, PDE8, and PDE10. Each subtype has distinct regulatory and catalytic properties, allowing for specific regulation of cyclic AMP levels in different cellular compartments and signaling pathways.

Inhibition of these enzymes can lead to an increase in intracellular cyclic AMP levels, which can have therapeutic effects in various diseases, such as cardiovascular disease, pulmonary hypertension, and central nervous system disorders. Therefore, PDE inhibitors are a valuable class of drugs for the treatment of these conditions.

Cyclic nucleotide phosphodiesterases (PDEs) are a family of enzymes that regulate intracellular levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which are important second messengers involved in various cellular processes.

Type 4 phosphodiesterases (PDE4) specifically hydrolyze cAMP and play a crucial role in regulating its intracellular concentration. PDE4 is widely expressed in many tissues, including the brain, heart, lungs, and immune system. It is involved in various physiological functions such as smooth muscle relaxation, neurotransmission, and inflammation.

PDE4 inhibitors have been developed as therapeutic agents for a variety of diseases, including asthma, chronic obstructive pulmonary disease (COPD), and depression. These drugs work by increasing intracellular cAMP levels, which can lead to bronchodilation, anti-inflammatory effects, and mood regulation. However, PDE4 inhibitors may also have side effects such as nausea, vomiting, and diarrhea, which limit their clinical use.

Cyclic nucleotide phosphodiesterases (PDEs) are a family of enzymes that regulate intracellular levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which are important second messengers involved in various cellular processes.

Type 3 PDEs, also known as PDE3, are a subtype of this enzyme family that specifically hydrolyze cAMP and cGMP. They are widely expressed in various tissues, including the heart, vascular smooth muscle, platelets, and adipose tissue.

PDE3 plays a crucial role in regulating cardiovascular function, lipolysis, and insulin sensitivity. Inhibition of PDE3 has been shown to have positive inotropic and vasodilatory effects, making it a potential therapeutic target for the treatment of heart failure and pulmonary hypertension. Additionally, PDE3 inhibitors have been used as antiplatelet agents to prevent thrombosis.

There are two isoforms of PDE3, PDE3A and PDE3B, which differ in their tissue distribution and regulatory mechanisms. PDE3A is primarily expressed in the heart and vascular smooth muscle, while PDE3B is found in adipose tissue and insulin-sensitive cells.

Overall, the regulation of intracellular cAMP and cGMP levels by PDE3 plays a critical role in maintaining cardiovascular function, metabolism, and hemostasis.

Cyclic nucleotide phosphodiesterases (PDEs) are a family of enzymes that regulate intracellular levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which are important second messengers involved in various cellular processes.

Type 2 phosphodiesterases (PDE2) are a subtype of this family that specifically hydrolyze both cAMP and cGMP to their respective 5'-monophosphates, thereby reducing their intracellular concentrations. PDE2 enzymes are widely expressed in various tissues, including the brain, heart, and vasculature, where they play important roles in regulating signal transduction pathways.

PDE2 enzymes are composed of two regulatory subunits and one catalytic subunit, which contains the active site for phosphodiesterase activity. The regulatory subunits can bind to cGMP, leading to an increase in PDE2 activity towards both cAMP and cGMP. This unique property of PDE2 enzymes allows them to act as coincidence detectors that integrate signals from multiple second messenger pathways.

Inhibition of PDE2 has been shown to have therapeutic potential in various diseases, including cardiovascular disease, neurodegenerative disorders, and cancer. For example, PDE2 inhibitors have been shown to improve cardiac function, protect against ischemic injury, and enhance cognitive function in animal models. However, further research is needed to fully understand the therapeutic potential of PDE2 inhibition and its potential side effects.

Phosphoric diester hydrolases are a class of enzymes that catalyze the hydrolysis of phosphoric diester bonds. These enzymes are also known as phosphatases or nucleotidases. They play important roles in various biological processes, such as signal transduction, metabolism, and regulation of cellular activities.

Phosphoric diester hydrolases can be further classified into several subclasses based on their substrate specificity and catalytic mechanism. For example, alkaline phosphatases (ALPs) are a group of phosphoric diester hydrolases that preferentially hydrolyze phosphomonoester bonds in a variety of organic molecules, releasing phosphate ions and alcohols. On the other hand, nucleotidases are a subclass of phosphoric diester hydrolases that specifically hydrolyze the phosphodiester bonds in nucleotides, releasing nucleosides and phosphate ions.

Overall, phosphoric diester hydrolases are essential for maintaining the balance of various cellular processes by regulating the levels of phosphorylated molecules and nucleotides.

2,3'-Cyclic-nucleotide phosphodiesterases (PDEs) are a subclass of enzymes that belong to the family of phosphodiesterases. These enzymes are responsible for the hydrolysis of 2,3'-cyclic nucleotides, which are cyclic forms of nucleotides that act as second messengers in various cellular signaling pathways.

The two primary types of 2,3'-cyclic nucleotides are 2',3'-cGMP and 2',3'-cAMP, which are produced by the action of certain enzymes on their respective precursors, guanosine triphosphate (GTP) and adenosine triphosphate (ATP). These cyclic nucleotides play important roles in regulating various cellular processes, including metabolism, gene expression, and ion channel activity.

2,3'-Cyclic-nucleotide phosphodiesterases catalyze the hydrolysis of these cyclic nucleotides to their corresponding 5'-monophosphates, thereby terminating their signaling activity. There are several isoforms of 2,3'-cyclic-nucleotide PDEs that have been identified, each with distinct substrate specificities and regulatory properties.

Dysregulation of 2,3'-cyclic-nucleotide PDE activity has been implicated in various diseases, including cancer, cardiovascular disease, and neurological disorders. Therefore, these enzymes have emerged as important targets for the development of therapeutic agents that can modulate their activity and restore normal cellular function.

Cyclic nucleotides are formed by the intramolecular phosphoester bond between the phosphate group and the hydroxyl group at the 3'-carbon atom of the ribose sugar in a nucleotide. This creates a cyclic structure, specifically a cyclic phosphate. The most common cyclic nucleotides are cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). These molecules function as second messengers in cells, playing crucial roles in various cellular signaling pathways related to metabolism, gene expression, and cell differentiation. The levels of cAMP and cGMP are tightly regulated by the activities of enzymes such as adenylate cyclase and guanylate cyclase for their synthesis, and phosphodiesterases for their degradation.

Phosphodiesterase inhibitors (PDE inhibitors) are a class of drugs that work by blocking the action of phosphodiesterase enzymes, which are responsible for breaking down cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), two crucial intracellular signaling molecules.

By inhibiting these enzymes, PDE inhibitors increase the concentration of cAMP and cGMP in the cells, leading to a variety of effects depending on the specific type of PDE enzyme that is inhibited. These drugs have been used in the treatment of various medical conditions such as erectile dysfunction, pulmonary arterial hypertension, and heart failure.

Examples of PDE inhibitors include sildenafil (Viagra), tadalafil (Cialis), vardenafil (Levitra) for erectile dysfunction, and iloprost, treprostinil, and sildenafil for pulmonary arterial hypertension. It's important to note that different PDE inhibitors have varying levels of selectivity for specific PDE isoforms, which can result in different therapeutic effects and side effect profiles.

3',5'-Cyclic guanosine monophosphate (cGMP) phosphodiesterases are a group of enzymes that play a role in regulating the levels of cGMP, an important intracellular signaling molecule involved in various biological processes. These enzymes catalyze the hydrolysis of cGMP to 5'-GMP, thereby terminating cGMP-mediated signals within cells.

There are several isoforms of cGMP phosphodiesterases, which differ in their regulatory properties, substrate specificity, and cellular distribution. These enzymes can be activated or inhibited by various factors, including drugs, hormones, and neurotransmitters, and play a crucial role in modulating the activity of cGMP-dependent signaling pathways in different tissues and organs.

Dysregulation of cGMP phosphodiesterase activity has been implicated in various diseases, including cardiovascular disorders, pulmonary hypertension, neurodegenerative diseases, and cancer. Therefore, these enzymes are considered important targets for the development of novel therapeutic strategies for the treatment of these conditions.

Cyclic nucleotide phosphodiesterases (PDEs) are a family of enzymes that regulate intracellular levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) by catalyzing the hydrolysis of these second messenger molecules to their inactive forms. These signaling molecules play crucial roles in various cellular processes, including smooth muscle relaxation, cardiac contractility, and neurotransmission.

Type 5 PDEs (PDE5) are a subtype of this enzyme family that specifically hydrolyze cGMP. They are widely distributed in various tissues, including vascular smooth muscle, lung, platelets, and the corpus cavernosum of the penis. PDE5 is particularly important in the regulation of smooth muscle relaxation in the corpus cavernosum, where it plays a key role in the physiological response to sexual stimulation leading to penile erection.

PDE5 inhibitors, such as sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra), are commonly used to treat erectile dysfunction by increasing cGMP levels in the corpus cavernosum, thereby promoting smooth muscle relaxation and enhancing blood flow to the penis. These medications have also been investigated for their potential therapeutic benefits in other conditions, such as pulmonary arterial hypertension and benign prostatic hyperplasia.

Cyclic guanosine monophosphate (cGMP) is a important second messenger molecule that plays a crucial role in various biological processes within the human body. It is synthesized from guanosine triphosphate (GTP) by the enzyme guanylyl cyclase.

Cyclic GMP is involved in regulating diverse physiological functions, such as smooth muscle relaxation, cardiovascular function, and neurotransmission. It also plays a role in modulating immune responses and cellular growth and differentiation.

In the medical field, changes in cGMP levels or dysregulation of cGMP-dependent pathways have been implicated in various disease states, including pulmonary hypertension, heart failure, erectile dysfunction, and glaucoma. Therefore, pharmacological agents that target cGMP signaling are being developed as potential therapeutic options for these conditions.

Cyclic nucleotide phosphodiesterases (PDEs) are a family of enzymes that play a crucial role in regulating intracellular levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which are important second messengers involved in various cellular processes.

Type 7 PDEs, also known as PDE7, is a subtype of the PDE family that specifically hydrolyzes cAMP. PDE7 is primarily expressed in hematopoietic cells, including T lymphocytes, monocytes, and natural killer (NK) cells, and plays a critical role in regulating immune cell functions.

PDE7 has two isoforms, PDE7A and PDE7B, which are encoded by different genes but share similar structures and functions. These isoforms are differentially expressed in various tissues and cells, with PDE7A being more abundant in T lymphocytes and monocytes, while PDE7B is predominantly expressed in NK cells.

Inhibition of PDE7 has been shown to enhance cAMP signaling and modulate immune cell functions, suggesting that PDE7 inhibitors may have therapeutic potential for the treatment of various inflammatory and autoimmune diseases, as well as cancer.

Cyclic adenosine monophosphate (cAMP) is a key secondary messenger in many biological processes, including the regulation of metabolism, gene expression, and cellular excitability. It is synthesized from adenosine triphosphate (ATP) by the enzyme adenylyl cyclase and is degraded by the enzyme phosphodiesterase.

In the body, cAMP plays a crucial role in mediating the effects of hormones and neurotransmitters on target cells. For example, when a hormone binds to its receptor on the surface of a cell, it can activate a G protein, which in turn activates adenylyl cyclase to produce cAMP. The increased levels of cAMP then activate various effector proteins, such as protein kinases, which go on to regulate various cellular processes.

Overall, the regulation of cAMP levels is critical for maintaining proper cellular function and homeostasis, and abnormalities in cAMP signaling have been implicated in a variety of diseases, including cancer, diabetes, and neurological disorders.

Rolipram is not a medical term per se, but it is the name of a pharmaceutical compound. Rolipram is a selective inhibitor of phosphodiesterase-4 (PDE4), an enzyme that plays a role in regulating the body's inflammatory response and is involved in various cellular signaling pathways.

Rolipram has been investigated as a potential therapeutic agent for several medical conditions, including depression, asthma, chronic obstructive pulmonary disease (COPD), and Alzheimer's disease. However, its development as a drug has been hindered by issues related to its pharmacokinetics, such as poor bioavailability and a short half-life, as well as side effects like nausea and emesis.

Therefore, while Rolipram is an important compound in the field of pharmacology and has contributed significantly to our understanding of PDE4's role in various physiological processes, it is not typically used as a medical term to describe a specific disease or condition.

1-Methyl-3-isobutylxanthine is a chemical compound that belongs to the class of xanthines. It is a methylated derivative of xanthine and is commonly found in some types of tea, coffee, and chocolate. This compound acts as a non-selective phosphodiesterase inhibitor, which means it can increase the levels of intracellular cyclic AMP (cAMP) by preventing its breakdown.

In medical terms, 1-Methyl-3-isobutylxanthine is often used as a bronchodilator and a stimulant of central nervous system. It is also known to have diuretic properties. This compound is sometimes used in the treatment of asthma, COPD (chronic obstructive pulmonary disease), and other respiratory disorders.

It's important to note that 1-Methyl-3-isobutylxanthine can have side effects, including increased heart rate, blood pressure, and anxiety. It should be used under the supervision of a medical professional and its use should be carefully monitored to avoid potential adverse reactions.

I'm sorry for any confusion, but "Purinones" is not a recognized term in medical terminology. It seems there might be a spelling mistake or a misunderstanding of the term. If you meant "purines," I can provide a definition for that. Purines are heterocyclic aromatic organic compounds that form the basis of several important biomolecules, such as nucleotides and their derivatives found in DNA and RNA. If you had something different in mind, please provide clarification so I can give you an accurate and helpful response.

Isoenzymes, also known as isoforms, are multiple forms of an enzyme that catalyze the same chemical reaction but differ in their amino acid sequence, structure, and/or kinetic properties. They are encoded by different genes or alternative splicing of the same gene. Isoenzymes can be found in various tissues and organs, and they play a crucial role in biological processes such as metabolism, detoxification, and cell signaling. Measurement of isoenzyme levels in body fluids (such as blood) can provide valuable diagnostic information for certain medical conditions, including tissue damage, inflammation, and various diseases.

Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.

Calmodulin is a small, ubiquitous calcium-binding protein that plays a critical role in various intracellular signaling pathways. It functions as a calcium sensor, binding to and regulating the activity of numerous target proteins upon calcium ion (Ca^2+^) binding. Calmodulin is expressed in all eukaryotic cells and participates in many cellular processes, including muscle contraction, neurotransmitter release, gene expression, metabolism, and cell cycle progression.

The protein contains four EF-hand motifs that can bind Ca^2+^ ions. Upon calcium binding, conformational changes occur in the calmodulin structure, exposing hydrophobic surfaces that facilitate its interaction with target proteins. Calmodulin's targets include enzymes (such as protein kinases and phosphatases), ion channels, transporters, and cytoskeletal components. By modulating the activity of these proteins, calmodulin helps regulate essential cellular functions in response to changes in intracellular Ca^2+^ concentrations.

Calmodulin's molecular weight is approximately 17 kDa, and it consists of a single polypeptide chain with 148-150 amino acid residues. The protein can be found in both the cytoplasm and the nucleus of cells. In addition to its role as a calcium sensor, calmodulin has been implicated in various pathological conditions, including cancer, neurodegenerative diseases, and cardiovascular disorders.

An amino acid sequence is the specific order of amino acids in a protein or peptide molecule, formed by the linking of the amino group (-NH2) of one amino acid to the carboxyl group (-COOH) of another amino acid through a peptide bond. The sequence is determined by the genetic code and is unique to each type of protein or peptide. It plays a crucial role in determining the three-dimensional structure and function of proteins.

In the context of medicine and pharmacology, "kinetics" refers to the study of how a drug moves throughout the body, including its absorption, distribution, metabolism, and excretion (often abbreviated as ADME). This field is called "pharmacokinetics."

1. Absorption: This is the process of a drug moving from its site of administration into the bloodstream. Factors such as the route of administration (e.g., oral, intravenous, etc.), formulation, and individual physiological differences can affect absorption.

2. Distribution: Once a drug is in the bloodstream, it gets distributed throughout the body to various tissues and organs. This process is influenced by factors like blood flow, protein binding, and lipid solubility of the drug.

3. Metabolism: Drugs are often chemically modified in the body, typically in the liver, through processes known as metabolism. These changes can lead to the formation of active or inactive metabolites, which may then be further distributed, excreted, or undergo additional metabolic transformations.

4. Excretion: This is the process by which drugs and their metabolites are eliminated from the body, primarily through the kidneys (urine) and the liver (bile).

Understanding the kinetics of a drug is crucial for determining its optimal dosing regimen, potential interactions with other medications or foods, and any necessary adjustments for special populations like pediatric or geriatric patients, or those with impaired renal or hepatic function.

Cyclic nucleotide phosphodiesterases (PDEs) are a family of enzymes that play a crucial role in regulating intracellular levels of cyclic nucleotides, which are important second messengers in various cellular signaling pathways. Among the different types of PDEs, type 6 (PDE6) is specifically expressed in the photoreceptor cells of the retina and is involved in the visual signal transduction cascade.

PDE6 is composed of two catalytic subunits, PDE6α and PDE6β, which are arranged in a heterodimeric complex. These subunits have distinct roles in the enzyme's activity: PDE6α contains the catalytic site that hydrolyzes cyclic guanosine monophosphate (cGMP) to GMP, while PDE6β regulates the activity of PDE6α through its inhibitory γ subunit.

In the visual signal transduction pathway, light stimulation leads to the activation of rhodopsin, which triggers a cascade of events that ultimately results in the hydrolysis of cGMP by PDE6. This reduction in cGMP levels causes the closure of cyclic nucleotide-gated channels in the plasma membrane, leading to hyperpolarization of the photoreceptor cells and the transmission of visual signals to the brain.

Defects in PDE6 have been implicated in various retinal disorders, including congenital stationary night blindness, retinitis pigmentosa, and age-related macular degeneration. Therefore, understanding the structure and function of PDE6 is essential for developing novel therapeutic strategies to treat these vision-threatening diseases.

Nucleotides are the basic structural units of nucleic acids, such as DNA and RNA. They consist of a nitrogenous base (adenine, guanine, cytosine, thymine or uracil), a pentose sugar (ribose in RNA and deoxyribose in DNA) and one to three phosphate groups. Nucleotides are linked together by phosphodiester bonds between the sugar of one nucleotide and the phosphate group of another, forming long chains known as polynucleotides. The sequence of these nucleotides determines the genetic information carried in DNA and RNA, which is essential for the functioning, reproduction and survival of all living organisms.

Phosphodiesterase 3 (PDE3) inhibitors are a class of medications that work by blocking the enzyme phosphodiesterase 3, which is responsible for breaking down cyclic adenosine monophosphate (cAMP) in the body. cAMP is a secondary messenger involved in various cellular processes such as regulation of heart function, vascular smooth muscle relaxation, and metabolism.

By inhibiting PDE3, these medications increase the levels of cAMP in the body, leading to vasodilation (relaxation of blood vessels), positive inotropic effects (improvement of heart contractility), and increased lipolysis (breakdown of fats). As a result, PDE3 inhibitors are used in the treatment of conditions such as heart failure, pulmonary hypertension, and peripheral vascular disease.

Examples of PDE3 inhibitors include cilostazol, milrinone, and enoximone.

Phosphodiesterase 4 inhibitors (PDE4 inhibitors) are a class of drugs that work by increasing the levels of cyclic adenosine monophosphate (cAMP) in cells. They do this by blocking the phosphodiesterase 4 enzyme, which is responsible for breaking down cAMP.

Cyclic AMP is an important intracellular signaling molecule that plays a role in various physiological processes, including inflammation and immune response. By increasing cAMP levels, PDE4 inhibitors can help to reduce inflammation and modulate the immune system.

PDE4 inhibitors have been studied for their potential therapeutic benefits in a range of conditions, including asthma, COPD, psoriasis, atopic dermatitis, and depression. Some examples of PDE4 inhibitors include roflumilast, apremilast, crisaborole, and ditropan.

It's important to note that while PDE4 inhibitors have shown promise in clinical trials, they can also have side effects, such as gastrointestinal symptoms, headache, and dizziness. Additionally, their long-term safety and efficacy are still being studied.

Dibutyryl cyclic guanosine monophosphate (cAMP) is a chemically modified form of the second messenger molecule, cyclic GMP (guanosine monophosphate). The addition of butyryl groups to the cyclic GMP molecule makes it more lipid-soluble and allows for easier passage through cell membranes. This compound is often used in research to activate protein kinases and study the effects of increased intracellular levels of cyclic GMP, which plays a role in various cellular processes such as smooth muscle relaxation, regulation of ion channels, and inhibition of platelet aggregation.

Theophylline is a medication that belongs to a class of drugs called methylxanthines. It is used in the management of respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and other conditions that cause narrowing of the airways in the lungs.

Theophylline works by relaxing the smooth muscle around the airways, which helps to open them up and make breathing easier. It also acts as a bronchodilator, increasing the flow of air into and out of the lungs. Additionally, theophylline has anti-inflammatory effects that can help reduce swelling in the airways and relieve symptoms such as coughing, wheezing, and shortness of breath.

Theophylline is available in various forms, including tablets, capsules, and liquid solutions. It is important to take this medication exactly as prescribed by a healthcare provider, as the dosage may vary depending on individual factors such as age, weight, and liver function. Regular monitoring of blood levels of theophylline is also necessary to ensure safe and effective use of the medication.

Phosphodiesterase I (PDE1) is an enzyme that belongs to the family of phosphodiesterase enzymes, which are responsible for breaking down cyclic nucleotides, such as cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), into their inactive forms. These cyclic nucleotides act as second messengers in various cellular signaling pathways, and their levels are tightly regulated by the balance between synthesis and degradation by enzymes like PDE1.

PDE1 is further classified into three subtypes: PDE1A, PDE1B, and PDE1C. These subtypes have different expression patterns and functions in various tissues and organs. For example, PDE1 is found in the brain, heart, smooth muscle, and other tissues, where it plays a role in regulating vascular tone, neurotransmission, and other physiological processes.

Inhibition of PDE1 has been explored as a potential therapeutic strategy for various conditions, including cardiovascular diseases, neurological disorders, and erectile dysfunction. However, the development of selective and specific PDE1 inhibitors has proven to be challenging due to the high degree of homology among different PDE subtypes.

Cyclic nucleotide-gated (CNG) channels are a type of ion channel found in the membranes of certain cells, particularly in the sensory neurons of the visual and olfactory systems. They are called cyclic nucleotide-gated because they can be activated or regulated by the binding of cyclic nucleotides, such as cyclic adenosine monophosphate (cAMP) or cyclic guanosine monophosphate (cGMP), to the intracellular domain of the channel.

CNG channels are permeable to cations, including sodium (Na+) and calcium (Ca2+) ions, and their activation allows these ions to flow into the cell. This influx of cations can trigger a variety of cellular responses, such as the initiation of visual or olfactory signaling pathways.

CNG channels are composed of four subunits that form a functional channel. Each subunit has a cyclic nucleotide-binding domain (CNBD) in its intracellular region, which can bind to cyclic nucleotides and regulate the opening and closing of the channel. The CNBD is connected to the pore-forming region of the channel by a flexible linker, allowing for conformational changes in the CNBD to be transmitted to the pore and modulate ion conductance.

CNG channels play important roles in various physiological processes, including sensory perception, neurotransmission, and cellular signaling. Dysfunction of CNG channels has been implicated in several human diseases, such as retinitis pigmentosa, congenital stationary night blindness, and cystic fibrosis.

Phosphorus-Oxygen Lyases are a class of enzymes that catalyze the breakdown of a substrate containing a phosphorus-oxygen bond, releasing a phosphate group and forming a new double bond in the process. This reaction is typically represented by the general formula:

Substrate-P-O + A acceptor ------> Substrate-O=A + P\_i

where "Substrate-P-O" represents the phosphorus-oxygen bond in the substrate, "A acceptor" is the molecule that accepts the phosphate group, and "P\_i" denotes inorganic phosphate. These enzymes play important roles in various biological processes, such as signal transduction, energy metabolism, and biosynthesis.

Examples of Phosphorus-Oxygen Lyases include:

1. Phospholipase D - catalyzes the hydrolysis of phosphatidylcholine to produce phosphatidic acid and choline.
2. ATP sulfurylase - catalyzes the formation of adenosine 5'-phosphosulfate (APS) from ATP and sulfate, which is an important intermediate in the biosynthesis of sulfur-containing amino acids.
3. Inositol polyphosphate 1-phosphatase - catalyzes the dephosphorylation of inositol polyphosphates, which are involved in intracellular signaling pathways.
4. UDP-glucose pyrophosphorylase - catalyzes the reversible conversion of UDP-glucose and pyrophosphate to glucose-1-phosphate and UTP, playing a crucial role in carbohydrate metabolism.

It is important to note that Phosphorus-Oxygen Lyases are distinct from Phosphoric Monoester Hydrolases, which also catalyze the hydrolysis of phosphorus-oxygen bonds but do not form new double bonds in the process.

Milrinone is a type of medication known as an inotrope and vasodilator. It works by increasing the force of heart muscle contractions and relaxing the blood vessels, which leads to improved pumping ability of the heart and increased blood flow. Milrinone is primarily used in the treatment of heart failure, either in the hospital setting or after discharge, to improve symptoms and help the heart work more efficiently. It is given intravenously (through an IV) and its effects are closely monitored by healthcare professionals due to the potential for serious side effects such as irregular heart rhythms.

I apologize for the confusion, but "Bucladesine" is not a recognized medical term or a medication in current use in medicine. It's possible that there may be some mistake or typo in the spelling. If you have any more context about where you encountered this term, I might be able to provide a more accurate and helpful response.

Pyrrolidinones are a class of organic compounds that contain a pyrrolidinone ring, which is a five-membered ring containing four carbon atoms and one nitrogen atom. The nitrogen atom is part of an amide functional group, which consists of a carbonyl (C=O) group bonded to a nitrogen atom.

Pyrrolidinones are commonly found in various natural and synthetic compounds, including pharmaceuticals, agrochemicals, and materials. They exhibit a wide range of biological activities, such as anti-inflammatory, antiviral, and anticancer properties. Some well-known drugs that contain pyrrolidinone rings include the pain reliever tramadol, the muscle relaxant cyclobenzaprine, and the antipsychotic aripiprazole.

Pyrrolidinones can be synthesized through various chemical reactions, such as the cyclization of γ-amino acids or the reaction of α-amino acids with isocyanates. The unique structure and reactivity of pyrrolidinones make them valuable intermediates in organic synthesis and drug discovery.

Adenine nucleotides are molecules that consist of a nitrogenous base called adenine, which is linked to a sugar molecule (ribose in the case of adenosine monophosphate or AMP, and deoxyribose in the case of adenosine diphosphate or ADP and adenosine triphosphate or ATP) and one, two, or three phosphate groups. These molecules play a crucial role in energy transfer and metabolism within cells.

AMP contains one phosphate group, while ADP contains two phosphate groups, and ATP contains three phosphate groups. When a phosphate group is removed from ATP, energy is released, which can be used to power various cellular processes such as muscle contraction, nerve impulse transmission, and protein synthesis. The reverse reaction, in which a phosphate group is added back to ADP or AMP to form ATP, requires energy input and often involves the breakdown of nutrients such as glucose or fatty acids.

In addition to their role in energy metabolism, adenine nucleotides also serve as precursors for other important molecules, including DNA and RNA, coenzymes, and signaling molecules.

Cyclic AMP (cAMP)-dependent protein kinases, also known as protein kinase A (PKA), are a family of enzymes that play a crucial role in intracellular signaling pathways. These enzymes are responsible for the regulation of various cellular processes, including metabolism, gene expression, and cell growth and differentiation.

PKA is composed of two regulatory subunits and two catalytic subunits. When cAMP binds to the regulatory subunits, it causes a conformational change that leads to the dissociation of the catalytic subunits. The freed catalytic subunits then phosphorylate specific serine and threonine residues on target proteins, thereby modulating their activity.

The cAMP-dependent protein kinases are activated in response to a variety of extracellular signals, such as hormones and neurotransmitters, that bind to G protein-coupled receptors (GPCRs) or receptor tyrosine kinases (RTKs). These signals lead to the activation of adenylyl cyclase, which catalyzes the conversion of ATP to cAMP. The resulting increase in intracellular cAMP levels triggers the activation of PKA and the downstream phosphorylation of target proteins.

Overall, cAMP-dependent protein kinases are essential regulators of many fundamental cellular processes and play a critical role in maintaining normal physiology and homeostasis. Dysregulation of these enzymes has been implicated in various diseases, including cancer, diabetes, and neurological disorders.

Cyclic guanosine monophosphate (cGMP)-dependent protein kinases (PKGs) are a type of enzyme that add phosphate groups to other proteins, thereby modifying their function. These kinases are activated by cGMP, which is a second messenger molecule that helps transmit signals within cells. PKGs play important roles in various cellular processes, including smooth muscle relaxation, platelet aggregation, and cardiac contractility. They have been implicated in the regulation of a number of physiological functions, such as blood flow, inflammation, and learning and memory. There are two main isoforms of cGMP-dependent protein kinases, PKG I and PKG II, which differ in their tissue distribution, regulatory properties, and substrate specificity.

Adenylate cyclase is an enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP). It plays a crucial role in various cellular processes, including signal transduction and metabolism. Adenylate cyclase is activated by hormones and neurotransmitters that bind to G-protein-coupled receptors on the cell membrane, leading to the production of cAMP, which then acts as a second messenger to regulate various intracellular responses. There are several isoforms of adenylate cyclase, each with distinct regulatory properties and subcellular localization.

Second messenger systems are a type of intracellular signaling pathway that allows cells to respond to external signals, such as hormones and neurotransmitters. When an extracellular signal binds to a specific receptor on the cell membrane, it activates a G-protein or an enzyme associated with the receptor. This activation leads to the production of a second messenger molecule inside the cell, which then propagates the signal and triggers various intracellular responses.

Examples of second messengers include cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), inositol trisphosphate (IP3), diacylglycerol (DAG), and calcium ions (Ca2+). These second messengers activate or inhibit various downstream effectors, such as protein kinases, ion channels, and gene transcription factors, leading to changes in cellular functions, such as metabolism, gene expression, cell growth, differentiation, and apoptosis.

Second messenger systems play crucial roles in many physiological processes, including sensory perception, neurotransmission, hormonal regulation, immune response, and development. Dysregulation of these systems can contribute to various diseases, such as cancer, diabetes, cardiovascular disease, and neurological disorders.

Papaverine is defined as a smooth muscle relaxant and a non-narcotic alkaloid derived from the opium poppy. It works by blocking the phosphodiesterase enzyme, leading to an increase in cyclic adenosine monophosphate (cAMP) levels within the cells, which in turn results in muscle relaxation.

It is used medically for its vasodilatory effects to treat conditions such as cerebral or peripheral vascular spasms and occlusive diseases, Raynaud's phenomenon, and priapism. Papaverine can also be used as an anti-arrhythmic agent in the management of certain types of cardiac arrhythmias.

It is important to note that papaverine has a narrow therapeutic index, and its use should be closely monitored due to the potential for adverse effects such as hypotension, reflex tachycardia, and gastrointestinal disturbances.

I'm not able to find a medical definition for "Cyclic IMP" in standard medical resources. It is possible that "Cyclic IMP" could be a specific term used within a certain medical context, such as in a research study or a medical specialty.

IMP is an abbreviation that can stand for several things in the medical field, including:

* Inosine Monophosphate, a nucleotide involved in the synthesis of DNA and RNA
* Imipenem, an antibiotic used to treat severe bacterial infections
* Ischemic Myocardial Pathology, a term used to describe damage to the heart muscle caused by reduced blood flow.

Without more context or information, it is difficult for me to provide a more specific definition of "Cyclic IMP." I would recommend consulting with a medical professional or checking the source where you encountered this term for further clarification.

A base sequence in the context of molecular biology refers to the specific order of nucleotides in a DNA or RNA molecule. In DNA, these nucleotides are adenine (A), guanine (G), cytosine (C), and thymine (T). In RNA, uracil (U) takes the place of thymine. The base sequence contains genetic information that is transcribed into RNA and ultimately translated into proteins. It is the exact order of these bases that determines the genetic code and thus the function of the DNA or RNA molecule.

Colforsin is a drug that belongs to a class of medications called phosphodiesterase inhibitors. It works by increasing the levels of a chemical called cyclic AMP (cyclic adenosine monophosphate) in the body, which helps to relax and widen blood vessels.

Colforsin is not approved for use in humans in many countries, including the United States. However, it has been used in research settings to study its potential effects on heart function and other physiological processes. In animals, colforsin has been shown to have positive inotropic (contractility-enhancing) and lusitropic (relaxation-enhancing) effects on the heart, making it a potential therapeutic option for heart failure and other cardiovascular conditions.

It is important to note that while colforsin has shown promise in preclinical studies, more research is needed to establish its safety and efficacy in humans. Therefore, it should only be used under the supervision of a qualified healthcare professional and in the context of a clinical trial or research study.

Guanylate cyclase is an enzyme that catalyzes the conversion of guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP), which acts as a second messenger in various cellular signaling pathways. There are two main types of guanylate cyclases: soluble and membrane-bound. Soluble guanylate cyclase is activated by nitric oxide, while membrane-bound guanylate cyclase can be activated by natriuretic peptides. The increased levels of cGMP produced by guanylate cyclase can lead to a variety of cellular responses, including smooth muscle relaxation, neurotransmitter release, and regulation of ion channels. Dysregulation of guanylate cyclase activity has been implicated in several diseases, such as hypertension, heart failure, and cancer.

Molecular cloning is a laboratory technique used to create multiple copies of a specific DNA sequence. This process involves several steps:

1. Isolation: The first step in molecular cloning is to isolate the DNA sequence of interest from the rest of the genomic DNA. This can be done using various methods such as PCR (polymerase chain reaction), restriction enzymes, or hybridization.
2. Vector construction: Once the DNA sequence of interest has been isolated, it must be inserted into a vector, which is a small circular DNA molecule that can replicate independently in a host cell. Common vectors used in molecular cloning include plasmids and phages.
3. Transformation: The constructed vector is then introduced into a host cell, usually a bacterial or yeast cell, through a process called transformation. This can be done using various methods such as electroporation or chemical transformation.
4. Selection: After transformation, the host cells are grown in selective media that allow only those cells containing the vector to grow. This ensures that the DNA sequence of interest has been successfully cloned into the vector.
5. Amplification: Once the host cells have been selected, they can be grown in large quantities to amplify the number of copies of the cloned DNA sequence.

Molecular cloning is a powerful tool in molecular biology and has numerous applications, including the production of recombinant proteins, gene therapy, functional analysis of genes, and genetic engineering.

Single Nucleotide Polymorphism (SNP) is a type of genetic variation that occurs when a single nucleotide (A, T, C, or G) in the DNA sequence is altered. This alteration must occur in at least 1% of the population to be considered a SNP. These variations can help explain why some people are more susceptible to certain diseases than others and can also influence how an individual responds to certain medications. SNPs can serve as biological markers, helping scientists locate genes that are associated with disease. They can also provide information about an individual's ancestry and ethnic background.

Phosphodiesterase 5 (PDE5) inhibitors are a class of medications that work by blocking the phosphodiesterase enzyme, specifically PDE5, which is found in the smooth muscle cells lining the blood vessels of the penis. By inhibiting this enzyme, PDE5 inhibitors increase the levels of cyclic guanosine monophosphate (cGMP), a molecule that relaxes these smooth muscles and allows for increased blood flow into the corpus cavernosum of the penis, leading to an erection.

PDE5 inhibitors are commonly used in the treatment of erectile dysfunction (ED) and include medications such as sildenafil (Viagra), tadalafil (Cialis), vardenafil (Levitra), and avanafil (Stendra). These medications are usually taken orally, and their effects can last for several hours. It is important to note that PDE5 inhibitors only work in the presence of sexual stimulation, and they do not increase sexual desire or arousal on their own.

In addition to their use in ED, PDE5 inhibitors have also been shown to be effective in the treatment of pulmonary arterial hypertension (PAH) by relaxing the smooth muscle cells in the blood vessels of the lungs and reducing the workload on the heart.

8-Bromo Cyclic Adenosine Monophosphate (8-Br-cAMP) is a synthetic, cell-permeable analog of cyclic adenosine monophosphate (cAMP). Cyclic AMP is an important second messenger in many signal transduction pathways, and 8-Br-cAMP is often used in research to mimic or study the effects of increased cAMP levels. The bromine atom at the 8-position makes 8-Br-cAMP more resistant to degradation by phosphodiesterases, allowing it to have a longer duration of action compared to cAMP. It is used in various biochemical and cellular studies as a tool compound to investigate the role of cAMP in different signaling pathways.

Calcium is an essential mineral that is vital for various physiological processes in the human body. The medical definition of calcium is as follows:

Calcium (Ca2+) is a crucial cation and the most abundant mineral in the human body, with approximately 99% of it found in bones and teeth. It plays a vital role in maintaining structural integrity, nerve impulse transmission, muscle contraction, hormonal secretion, blood coagulation, and enzyme activation.

Calcium homeostasis is tightly regulated through the interplay of several hormones, including parathyroid hormone (PTH), calcitonin, and vitamin D. Dietary calcium intake, absorption, and excretion are also critical factors in maintaining optimal calcium levels in the body.

Hypocalcemia refers to low serum calcium levels, while hypercalcemia indicates high serum calcium levels. Both conditions can have detrimental effects on various organ systems and require medical intervention to correct.

Guanine nucleotides are molecules that play a crucial role in intracellular signaling, cellular regulation, and various biological processes within cells. They consist of a guanine base, a sugar (ribose or deoxyribose), and one or more phosphate groups. The most common guanine nucleotides are GDP (guanosine diphosphate) and GTP (guanosine triphosphate).

GTP is hydrolyzed to GDP and inorganic phosphate by certain enzymes called GTPases, releasing energy that drives various cellular functions such as protein synthesis, signal transduction, vesicle transport, and cell division. On the other hand, GDP can be rephosphorylated back to GTP by nucleotide diphosphate kinases, allowing for the recycling of these molecules within the cell.

In addition to their role in signaling and regulation, guanine nucleotides also serve as building blocks for RNA (ribonucleic acid) synthesis during transcription, where they pair with cytosine nucleotides via hydrogen bonds to form base pairs in the resulting RNA molecule.

"Cattle" is a term used in the agricultural and veterinary fields to refer to domesticated animals of the genus *Bos*, primarily *Bos taurus* (European cattle) and *Bos indicus* (Zebu). These animals are often raised for meat, milk, leather, and labor. They are also known as bovines or cows (for females), bulls (intact males), and steers/bullocks (castrated males). However, in a strict medical definition, "cattle" does not apply to humans or other animals.

Hydrolysis is a chemical process, not a medical one. However, it is relevant to medicine and biology.

Hydrolysis is the breakdown of a chemical compound due to its reaction with water, often resulting in the formation of two or more simpler compounds. In the context of physiology and medicine, hydrolysis is a crucial process in various biological reactions, such as the digestion of food molecules like proteins, carbohydrates, and fats. Enzymes called hydrolases catalyze these hydrolysis reactions to speed up the breakdown process in the body.

Isoproterenol is a medication that belongs to a class of drugs called beta-adrenergic agonists. Medically, it is defined as a synthetic catecholamine with both alpha and beta adrenergic receptor stimulating properties. It is primarily used as a bronchodilator to treat conditions such as asthma and chronic obstructive pulmonary disease (COPD) by relaxing the smooth muscles in the airways, thereby improving breathing.

Isoproterenol can also be used in the treatment of bradycardia (abnormally slow heart rate), cardiac arrest, and heart blocks by increasing the heart rate and contractility. However, due to its non-selective beta-agonist activity, it may cause various side effects such as tremors, palpitations, and increased blood pressure. Its use is now limited due to the availability of more selective and safer medications.

Xanthines are a type of natural alkaloids that are found in various plants, including tea leaves, cocoa beans, and mate. The most common xanthines are caffeine, theophylline, and theobromine. These compounds have stimulant effects on the central nervous system and are often used in medication to treat conditions such as asthma, bronchitis, and other respiratory issues.

Caffeine is the most widely consumed xanthine and is found in a variety of beverages like coffee, tea, and energy drinks. It works by blocking adenosine receptors in the brain, which can lead to increased alertness and reduced feelings of fatigue.

Theophylline is another xanthine that is used as a bronchodilator to treat asthma and other respiratory conditions. It works by relaxing smooth muscles in the airways, making it easier to breathe.

Theobromine is found in cocoa beans and is responsible for the stimulant effects of chocolate. While it has similar properties to caffeine and theophylline, it is less potent and has a milder effect on the body.

It's worth noting that while xanthines can have beneficial effects when used in moderation, they can also cause negative side effects such as insomnia, nervousness, and rapid heart rate if consumed in large quantities or over an extended period of time.

In the context of medical and biological sciences, a "binding site" refers to a specific location on a protein, molecule, or cell where another molecule can attach or bind. This binding interaction can lead to various functional changes in the original protein or molecule. The other molecule that binds to the binding site is often referred to as a ligand, which can be a small molecule, ion, or even another protein.

The binding between a ligand and its target binding site can be specific and selective, meaning that only certain ligands can bind to particular binding sites with high affinity. This specificity plays a crucial role in various biological processes, such as signal transduction, enzyme catalysis, or drug action.

In the case of drug development, understanding the location and properties of binding sites on target proteins is essential for designing drugs that can selectively bind to these sites and modulate protein function. This knowledge can help create more effective and safer therapeutic options for various diseases.

A catalytic domain is a portion or region within a protein that contains the active site, where the chemical reactions necessary for the protein's function are carried out. This domain is responsible for the catalysis of biological reactions, hence the name "catalytic domain." The catalytic domain is often composed of specific amino acid residues that come together to form the active site, creating a unique three-dimensional structure that enables the protein to perform its specific function.

In enzymes, for example, the catalytic domain contains the residues that bind and convert substrates into products through chemical reactions. In receptors, the catalytic domain may be involved in signal transduction or other regulatory functions. Understanding the structure and function of catalytic domains is crucial to understanding the mechanisms of protein function and can provide valuable insights for drug design and therapeutic interventions.

Signal transduction is the process by which a cell converts an extracellular signal, such as a hormone or neurotransmitter, into an intracellular response. This involves a series of molecular events that transmit the signal from the cell surface to the interior of the cell, ultimately resulting in changes in gene expression, protein activity, or metabolism.

The process typically begins with the binding of the extracellular signal to a receptor located on the cell membrane. This binding event activates the receptor, which then triggers a cascade of intracellular signaling molecules, such as second messengers, protein kinases, and ion channels. These molecules amplify and propagate the signal, ultimately leading to the activation or inhibition of specific cellular responses.

Signal transduction pathways are highly regulated and can be modulated by various factors, including other signaling molecules, post-translational modifications, and feedback mechanisms. Dysregulation of these pathways has been implicated in a variety of diseases, including cancer, diabetes, and neurological disorders.

Vinca alkaloids are a group of naturally occurring chemicals derived from the Madagascar periwinkle plant, Catharanthus roseus. They are known for their antineoplastic (cancer-fighting) properties and are used in chemotherapy to treat various types of cancer. Some examples of vinca alkaloids include vinblastine, vincristine, and vinorelbine. These agents work by disrupting the normal function of microtubules, which are important components of the cell's structure and play a critical role in cell division. By binding to tubulin, a protein that makes up microtubules, vinca alkaloids prevent the formation of mitotic spindles, which are necessary for cell division. This leads to cell cycle arrest and apoptosis (programmed cell death) in cancer cells. However, vinca alkaloids can also affect normal cells, leading to side effects such as neurotoxicity, myelosuppression, and gastrointestinal disturbances.

Cyclic peroxides, often referred to as cyclic peroxide compounds, are organic substances that contain a ring structure formed by two oxygen atoms bonded together (a peroxide group) and one or more hydrocarbon chains. These compounds can be found in various chemical and biological systems, including some natural products and synthetic materials.

Cyclic peroxides have potential applications in several areas, such as pharmaceuticals, agrochemicals, and polymer chemistry. However, they are also known to be potentially unstable and may decompose under certain conditions, releasing oxygen gas and generating free radicals that can cause oxidative damage to other molecules. Therefore, handling and storing cyclic peroxides require caution and appropriate safety measures.

It is worth noting that the term "P-Oxides" in the question may be a typo or a shorthand for "peroxides," as "P" does not have any specific meaning in this context.

Enzyme activation refers to the process by which an enzyme becomes biologically active and capable of carrying out its specific chemical or biological reaction. This is often achieved through various post-translational modifications, such as proteolytic cleavage, phosphorylation, or addition of cofactors or prosthetic groups to the enzyme molecule. These modifications can change the conformation or structure of the enzyme, exposing or creating a binding site for the substrate and allowing the enzymatic reaction to occur.

For example, in the case of proteolytic cleavage, an inactive precursor enzyme, known as a zymogen, is cleaved into its active form by a specific protease. This is seen in enzymes such as trypsin and chymotrypsin, which are initially produced in the pancreas as inactive precursors called trypsinogen and chymotrypsinogen, respectively. Once they reach the small intestine, they are activated by enteropeptidase, a protease that cleaves a specific peptide bond, releasing the active enzyme.

Phosphorylation is another common mechanism of enzyme activation, where a phosphate group is added to a specific serine, threonine, or tyrosine residue on the enzyme by a protein kinase. This modification can alter the conformation of the enzyme and create a binding site for the substrate, allowing the enzymatic reaction to occur.

Enzyme activation is a crucial process in many biological pathways, as it allows for precise control over when and where specific reactions take place. It also provides a mechanism for regulating enzyme activity in response to various signals and stimuli, such as hormones, neurotransmitters, or changes in the intracellular environment.

Substrate specificity in the context of medical biochemistry and enzymology refers to the ability of an enzyme to selectively bind and catalyze a chemical reaction with a particular substrate (or a group of similar substrates) while discriminating against other molecules that are not substrates. This specificity arises from the three-dimensional structure of the enzyme, which has evolved to match the shape, charge distribution, and functional groups of its physiological substrate(s).

Substrate specificity is a fundamental property of enzymes that enables them to carry out highly selective chemical transformations in the complex cellular environment. The active site of an enzyme, where the catalysis takes place, has a unique conformation that complements the shape and charge distribution of its substrate(s). This ensures efficient recognition, binding, and conversion of the substrate into the desired product while minimizing unwanted side reactions with other molecules.

Substrate specificity can be categorized as:

1. Absolute specificity: An enzyme that can only act on a single substrate or a very narrow group of structurally related substrates, showing no activity towards any other molecule.
2. Group specificity: An enzyme that prefers to act on a particular functional group or class of compounds but can still accommodate minor structural variations within the substrate.
3. Broad or promiscuous specificity: An enzyme that can act on a wide range of structurally diverse substrates, albeit with varying catalytic efficiencies.

Understanding substrate specificity is crucial for elucidating enzymatic mechanisms, designing drugs that target specific enzymes or pathways, and developing biotechnological applications that rely on the controlled manipulation of enzyme activities.

Sequence homology, amino acid, refers to the similarity in the order of amino acids in a protein or a portion of a protein between two or more species. This similarity can be used to infer evolutionary relationships and functional similarities between proteins. The higher the degree of sequence homology, the more likely it is that the proteins are related and have similar functions. Sequence homology can be determined through various methods such as pairwise alignment or multiple sequence alignment, which compare the sequences and calculate a score based on the number and type of matching amino acids.

2007). "Cyclic nucleotide phosphodiesterase PDE1C1 in human cardiac myocytes". J. Biol. Chem. 282 (45): 32749-57. doi:10.1074/ ... 2006). "Subcellular localization and regulation of type-1C and type-5 phosphodiesterases". Biochem. Biophys. Res. Commun. 341 ( ... Rybalkin SD, Rybalkina I, Beavo JA, Bornfeldt KE (2002). "Cyclic nucleotide phosphodiesterase 1C promotes human arterial smooth ... cyclic nucleotide phosphodiesterase 1C is an enzyme that in humans is encoded by the PDE1C gene. GRCh38: Ensembl release 89: ...
"Differential activation and inhibition of the multiple forms of cyclic nucleotide phosphodiesterase". Advances in Cyclic ... Cyclic guanosine monophosphate-specific phosphodiesterase type 5 is an enzyme (EC 3.1.4.17) from the phosphodiesterase class. ... Fertel R, Weiss B (July 1976). "Properties and drug responsiveness of cyclic nucleotide phosphodiesterases of rat lung" ( ... Weiss B, Hait WN (1977). "Selective cyclic nucleotide phosphodiesterase inhibitors as potential therapeutic agents". Annual ...
The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE4 subfamily. This PDE ... "Pivotal role of cyclic nucleoside phosphodiesterase 4 in Tat-mediated CD4+ T cell hyperactivation and HIV type 1 replication". ... Zhou L, Thompson WJ, Potter DE (Jul 1999). "Multiple cyclic nucleotide phosphodiesterases in human trabecular meshwork cells" ( ... of a human cytosolic type-IVA, cyclic AMP specific phosphodiesterase (hPDE-IVA-h6.1)". Cellular Signalling. 6 (7): 793-812. doi ...
... cyclic nucleotide phosphodiesterases ARF1 (ADP Ribosylation factor 1) A type (Kv4.3; Shal-related subfamily, member 3) voltage- ... The designation 'NCS-1' came from the assumption that the protein was expressed only in neuronal cell types, which is not the ... type III phosphatidylinositol 4-kinase β) IP3 receptor (this activity is inhibited by lithium - a drug used for the treatment ... 5 (5): e10534. Bibcode:2010PLoSO...510534H. doi:10.1371/journal.pone.0010534. PMC 2866544. PMID 20479890. Pongs O, Lindemeier J ...
"Cryo-EM structure of phosphodiesterase 6 reveals insights into the allosteric regulation of type I phosphodiesterases". Science ... cyclic-nucleotide phosphodiesterases (EC 3.1.4.17) are a family of phosphodiesterases. Generally, these enzymes hydrolyze a ... cyclic-nucleotide phosphodiesterases in rod cells are oligomeric, made up of two heavy catalytic subunits, α (90 kDa) and β (85 ... "Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use". Pharmacological Reviews. 58 (3): 488-520. doi: ...
Cyclic nucleotides can be found in many different types of eukaryotic cells, including photo-receptor rods and cones, smooth ... cAMP's role in this process terminates upon hydrolysis to AMP by phosphodiesterase. Cyclic nucleotides are well-suited to act ... The two most well-studied cyclic nucleotides are cyclic AMP (cAMP) and cyclic GMP (cGMP), while cyclic CMP (cCMP) and cyclic ... A cyclic nucleotide (cNMP) is a single-phosphate nucleotide with a cyclic bond arrangement between the sugar and phosphate ...
Lugnier, C. (2006). "Cyclic nucleotide phosphodiesterase (PDE) superfamily: A new target for the development of specific ... Yu, J. Y.; Kang, K. K. & Yoo, M. (2006). "Erectile potentials of a new phosphodiesterase type 5 inhibitor, DA-8159, in diet- ... Their function is to degrade intracellular second messengers such as cyclic adenine monophosphate (cAMP) and cyclic guanosine ... "Phosphodiesterase type-5 inhibitor use in type 2 diabetes is associated with a reduction in all-cause mortality". Heart. 102 ( ...
... by adenylyl cyclase and metabolized by cyclic nucleotide phosphodiesterases (PDEs). One manifestation of depression is an ... a type of glutamate receptor - produces rapid (within 2 hours), robust and sustained (lasting for up to a fortnight) ... "Interaction between the antidepressant-like behavioral effects of beta adrenergic agonists and the cyclic AMP PDE inhibitor ... system induced by different types of chronic but not acute antidepressant treatment, including serotonin and norepinephrine ...
It is one of many ubiquitous nucleotide second messengers including cyclic adenosine monophosphate (cAMP), cyclic guanosine ... "The helicase DDX41 recognizes the bacterial secondary messengers cyclic di-GMP and cyclic di-AMP to activate a type I ... Phosphodiesterase (PDE) enzymes degrade cyclic di-AMP to the linear molecule 5'-pApA (phosphadenylyl adenosine). 5'-pApA is ... "Cyclic nucleotides in archaea: Cyclic di-AMP in the archaeon Haloferax volcanii and its putative role". MicrobiologyOpen. 8 (9 ...
"Biochemistry and physiology of cyclic nucleotide phosphodiesterases: essential components in cyclic nucleotide signaling". ... Phosphodiesterase enzymes have been shown to be different in different types of cells, including normal and leukemic ... Usually, phosphodiesterase refers to cyclic nucleotide phosphodiesterases, which have great clinical significance and are ... "Differential activation and inhibition of the multiple forms of cyclic nucleotide phosphodiesterase". Advances in Cyclic ...
He is best known for his work with cyclic nucleotide phosphodiesterases. He was the first to propose, based on his experimental ... He showed that a single cell type may contain more than one form of phosphodiesterase [6,7] and that different forms of ... Cyclic Nucleotide Phosphodiesterases: Weiss and co-workers developed rapid phosphodiesterease assays [3, 4], separated ... Weiss, B. and Winchurch, R.A.: Analyses of cyclic nucleotide phosphodiesterases in lymphocytes from normal and aged leukemic ...
Essayan DM (November 2001). "Cyclic nucleotide phosphodiesterases". The Journal of Allergy and Clinical Immunology. 108 (5): ... Moreover, some patients may experience more than one type of psoriatic lesion and/or have lesions across multiple locations. ... Cannabinoid type 2 receptor-dependent and -independent immunomodulatory effects". The Journal of Biological Chemistry. 281 (20 ... "Binding and functional comparisons of two types of tumor necrosis factor antagonists". The Journal of Pharmacology and ...
September 2003). "Cyclic nucleotide phosphodiesterase activity, expression, and targeting in cells of the cardiovascular system ... PDE3A can be either membrane-associated or cytosolic, depending on the variant and the cell type it is expressed in. PDE3A and ... Lugnier C (March 2006). "Cyclic nucleotide phosphodiesterase (PDE) superfamily: a new target for the development of specific ... WO 03012030, Movsesian M, "Isoform-Selective Inhibitors and Activators of PDE3 Cyclic Nucleotide Phosphodiesterases", published ...
2003). "Comparison of enzymatic characterization and gene organization of cyclic nucleotide phosphodiesterase 8 family in ... 2003). "Alterations on phosphodiesterase type 7 and 8 isozyme mRNA expression in Alzheimer's disease brains examined by in situ ... cyclic nucleotide phosphodiesterase". Biochem Biophys Res Commun. 250 (3): 751-6. doi:10.1006/bbrc.1998.9379. PMID 9784418. " ... cyclic phosphodiesterase 8B is an enzyme that in humans is encoded by the PDE8B gene. GRCm38: Ensembl release 89: ...
This gene is a member of the type IV, cyclic AMP (cAMP)-specific, cyclic nucleotide phosphodiesterase (PDE) family. Cyclic ... The cyclic nucleotide phosphodiesterases (PDEs) regulate the cellular concentrations of cyclic nucleotides and thereby play a ... "Pivotal role of cyclic nucleoside phosphodiesterase 4 in Tat-mediated CD4+ T cell hyperactivation and HIV type 1 replication". ... "Entrez Gene: PDE4B phosphodiesterase 4B, cAMP-specific (phosphodiesterase E4 dunce homolog, Drosophila)". Swerdlow, Neal R. ( ...
1998). "Identification and characterization of a novel cyclic nucleotide phosphodiesterase gene (PDE9A) that maps to 21q22.3: ... "Identification and characterization of a new human type 9 cGMP-specific phosphodiesterase splice variant (PDE9A5). Differential ... cyclic phosphodiesterase 9A is an enzyme that in humans is encoded by the PDE9A gene. The protein encoded by this gene ... "Entrez Gene: PDE9A phosphodiesterase 9A". Verhoest PR, Fonseca KR, Hou X, et al. (2012). "Design and discovery of 6-[(3S,4S)-4- ...
In mammals, GAF domains are found in five members of the cyclic nucleotide phosphodiesterase superfamily: PDE2, PDE5, and PDE6 ... The GAF domain is a type of protein domain that is found in a wide range of proteins from all species. The GAF domain is named ... a ubiquitous signaling motif and a new class of cyclic GMP receptor". The EMBO Journal. 19 (20): 5288-99. doi:10.1093/emboj/ ... "The two GAF domains in phosphodiesterase 2A have distinct roles in dimerization and in cGMP binding". Proceedings of the ...
... cAMP binds to and regulates the function of ion channels such as the HCN channels and a few other cyclic nucleotide-binding ... cyclic monophosphate (8-Br-cAMP) Acrasin specific to chemotactic use in Dictyostelium discoideum. phosphodiesterase 4 (PDE 4) ... If a cell lacks GM1 the toxin most likely binds to other types of glycans, such as Lewis Y and Lewis X, attached to proteins ... such as cyclic adenosine monophosphate, cyclic AMP). Cyclic AMP is synthesized from ATP by adenylate cyclase located on the ...
Cyclic-nucleotide 3'-phosphodiesterase (CNPase) List of distinct cell types in the adult human body List of human cell types ... Oligodendrocytes are a type of glial cell. They arise during development from oligodendrocyte precursor cells (OPCs), which can ... Notably, oligodendrocytes are the last type of cell to be generated in the CNS. Oligodendrocytes were discovered by Pío del Río ... Oligodendrocytes (from Greek 'cells with a few branches'), also known as oligodendroglia, are a type of neuroglia whose main ...
"Functional and biochemical evidence for diazepam as a cyclic nucleotide phosphodiesterase type 4 inhibitor". British Journal of ... Barad M, Bourtchouladze R, Winder DG, Golan H, Kandel E (1998). "Rolipram, a type IV-specific phosphodiesterase inhibitor, ... Dinter, H (February 2000). "Phosphodiesterase type 4 inhibitors: potential in the treatment of multiple sclerosis?". BioDrugs. ... Moustafa, F; Feldman, SR (16 May 2014). "A Review of Phosphodiesterase-Inhibition and the Potential Role for Phosphodiesterase ...
Essayan DM (November 2001). "Cyclic nucleotide phosphodiesterases". The Journal of Allergy and Clinical Immunology. 108 (5): ... "Effect of pentoxifylline on diabetic distal polyneuropathy in type 2 diabetic patients: A randomized trial". Journal of ... Like other methylated xanthine derivatives, pentoxifylline is a competitive nonselective phosphodiesterase inhibitor which ... the effects of non-specific phosphodiesterase inhibition". Clinics. 63 (3): 321-328. doi:10.1590/S1807-59322008000300006. PMC ...
Sun L, Wu J, Du F, Chen X, Chen ZJ (February 2013). "Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type ... cGAMP was found to be much more potent than other cyclic di-nucleotides (c-di-GMP and c-di-AMP). cGAMP was shown to ... phosphodiesterases. Other advantages of the unique 2'-5' linkage may be that cGAMP is able to bind multiple allelic variants of ... Cyclic GMP-AMP (cGAMP) is a cyclic dinucleotide (CDN) and the first to be found in metazoans. Other CDNs (c-di-GMP and c-di-AMP ...
Cyclic-nucleotide 3'-phosphodiesterase. Moreover, oligodendrocytes also developed and migrated into fiber bundles in mice when ... Using doses between 1 μM to 3 μM of RA can generate neurons as the most abundant cell type. Neurons under this treatment ... The cell line is pluripotent and can differentiate into cell types of all three germ layers. Also, it is the most characterized ... At concentration of 0.5-1% DMSO induced P19 cells to aggregate and process mesodermal and endodermal cell types. The cellular ...
"Cryo-EM structure of phosphodiesterase 6 reveals insights into the allosteric regulation of type I phosphodiesterases". Science ... Journal of Cyclic Nucleotide Research. 2 (3): 139-48. PMID 6493. Keeler, CE (20 March 1928). "The Geotropic Reaction of Rodless ... "Cryo-EM structure of phosphodiesterase 6 reveals insights into the allosteric regulation of type I phosphodiesterases". Science ... cyclic phosphodiesterase subunit beta is the beta subunit of the protein complex PDE6 that is encoded by the PDE6B gene. PDE6 ...
Methylxanthines such as caffeine inhibit the action of cyclic nucleotide phosphodiesterase, which normally acts to break down ... Symptoms must also not have a more likely clinical cause, such as another type of anxiety disorder, come before the ingestion ... Cyclic adenosine monophosphate, or cAMP, is a second messenger important in many cellular processes and is a critical factor in ... Adenosine acts on A1 receptors to decrease opening of N-type Ca2+ channels in some hippocampal neurons, and therefore decrease ...
This compound is a potent inhibitor of cGMP specific phosphodiesterase type 5, the enzyme that degrades the signalling molecule ... This block of nucleotide biosynthesis is selectively toxic to rapidly growing cells, therefore methotrexate is often used in ... cyclic guanosine monophosphate. This signalling molecule triggers smooth muscle relaxation and allows blood flow into the ... 381-382 Although it is possible for mixed-type inhibitors to bind in the active site, this type of inhibition generally results ...
Weiss B, Hait WN (1977). "Selective cyclic nucleotide phosphodiesterase inhibitors as potential therapeutic agents". Annual ... A phosphodiesterase type 5 inhibitor (PDE5 inhibitor) is a vasodilating drug that works by blocking the degradative action of ... Differential Activation and Inhibition of the Multiple Forms of Cyclic Nucleotide Phosphodiesterase. pp. 195-211. ISBN 978-0- ... "Properties and drug responsiveness of cyclic nucleotide phosphodiesterases of rat lung". Molecular Pharmacology. 12 (4): 678-87 ...
... cyclic-GMP phosphodiesterase EC 3.1.4.36: Now with EC 3.1.4.43 EC 3.1.4.37: 2′,3′-cyclic-nucleotide 3'-phosphodiesterase EC 3.1 ... type I site-specific deoxyribonuclease EC 3.1.21.4: type II site-specific deoxyribonuclease EC 3.1.21.5: type III site-specific ... phosphodiesterase * EC 3.1.4.59: cyclic-di-AMP phosphodiesterase * EC 3.1.4.60: pApA phosphodiesterase * EC 3.1.4.61: cyclic 2, ... 2-cyclic phosphate phosphodiesterase * EC 3.1.4.56: 7,8-dihydroneopterin 2′,3′-cyclic phosphate phosphodiesterase EC 3.1.4.57: ...
2001). "Cyclic nucleotide phosphodiesterases". The Journal of Allergy and Clinical Immunology. 108 (5): 671-80. doi:10.1067/mai ... Jan 2012). "Neuroprotective efficacy of quinazoline type phosphodiesterase 7 inhibitors in cellular cultures and experimental ... Fertel R, Weiss B (1976). "Properties and drug responsiveness of cyclic nucleotide phosphodiesterases of rat lung". Mol. ... Weiss B (1975). "Differential activation and inhibition of the multiple forms of cyclic nucleotide phosphodiesterase". Adv. ...
Lugnier C (March 2006). "Cyclic nucleotide phosphodiesterase (PDE) superfamily: a new target for the development of specific ... The catalytic domains of phosphodiesterase 1 (and other types of phosphodiesterases) have three helical subdomains: an N- ... Kakkar R, Raju RV, Sharma RK (July 1999). "Calmodulin-dependent cyclic nucleotide phosphodiesterase (PDE1)". Cell. Mol. Life ... Bender AT, Beavo JA (September 2006). "Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use". Pharmacol. ...
2007). "Cyclic nucleotide phosphodiesterase PDE1C1 in human cardiac myocytes". J. Biol. Chem. 282 (45): 32749-57. doi:10.1074/ ... 2006). "Subcellular localization and regulation of type-1C and type-5 phosphodiesterases". Biochem. Biophys. Res. Commun. 341 ( ... Rybalkin SD, Rybalkina I, Beavo JA, Bornfeldt KE (2002). "Cyclic nucleotide phosphodiesterase 1C promotes human arterial smooth ... cyclic nucleotide phosphodiesterase 1C is an enzyme that in humans is encoded by the PDE1C gene. GRCh38: Ensembl release 89: ...
Recent progress in the field of cyclic nucleotides has shown that a large array of closely related proteins is involved in each ... The molecular biology of cyclic nucleotide phosphodiesterases Prog Nucleic Acid Res Mol Biol. 1999:63:1-38. doi: 10.1016/s0079- ... In mammals, 19 different genes encode the cyclic nucleotide phosphodiesterases (PDEs), the enzymes that hydrolyze and ... Publication types * Research Support, U.S. Govt, P.H.S. * Review MeSH terms * 3,5-Cyclic-AMP Phosphodiesterases / genetics* ...
... On-line free ... Peptides, Cyclic. 1. + 153. Cyclic Nucleotide Phosphodiesterases, Type 5. 1. + 154. Substance P. 1. + ... Tension-Type Headache; Headache, Tension; Psychogenic Headache; Stress Headache; Tension-Vascular Headache. Fast. Hierarchical ...
Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection ... Type 5 Cyclic Nucleotide Phosphodiesterases 100% * Sildenafil Citrate 76% * Heart Failure 50% ... Lavine, K. J., Kovacs, A., Weinheimer, C. & Mann, D. L., 2013, In: Journal of the American Heart Association. 2, 5, e000343.. ... 5, p. 988-997 10 p.. Research output: Contribution to journal › Article › peer-review ...
RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in HFpEF) was a multicenter randomized ... Patients with AF had higher N-terminal pro-B-type natriuretic peptide, aldosterone, endothelin-1, troponin I, and C-telopeptide ... RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in HFpEF) was a multicenter randomized ... RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in HFpEF) was a multicenter randomized ...
... tissue distributions and functions but that all exert their effect by lowering intracellular levels of cyclic nucleotides, such ... The types of medications can be divided into oral, topical, injectable, and intraurethrally inserted. Phosphodiesterase type 5 ... Phosphodiesterase-5 Enzyme Inhibitors. Class Summary. At least seven phosphodiesterase (PDE) classes are known, many with ... Identifying patients with type 2 diabetes with a higher likelihood of erectile dysfunction: the role of the interaction between ...
... phosphodiesterase 1B1, Ca2+-calmodulin dependent, 63 kDa; presumed 63kDa form of the type 1 cyclic nucleotide phosphodiesterase ... cyclic nucleotide phosphodiesterase 1B; calcium/calmodulin-stimulated cyclic nucleotide phosphodiesterase; calmodulin- ... cyclic-AMP phosphodiesterase activity calmodulin-dependent cyclic-nucleotide phosphodiesterase activity protein binding ... cyclic-GMP phosphodiesterase activity cyclic-nucleotide phosphodiesterase activity 3,5-cyclic-nucleotide phosphodiesterase ...
... particularly cyclic nucleotide phosphodiesterases (PDEs). MAIN METHODS: Type 1 diabetes (T1D) was induced in rats by ... Cardiac Phosphodiesterases Are Differentially Increased in Diabetic Cardiomyopathy. Hanna, Rita; Nour-Eldine, Wared; Saliba, ... Type 2 diabetes mellitus (T2DM) accounts for 90-95 % of worldwide diabetes cases and is primarily characterized by insulin ... Male, 20-week-old, Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type 2 diabetes model, were randomly divided into two ...
Among the 11 isoforms of phosphodiesterases (PDEs), the most important are the PDE3 and PDE5 isoforms, which degrade cyclic ... leading to the conversion of guanosine triphosphate nucleotide into cyclic guanosine monophosphate (cGMP). The increase in ... or nitric oxide synthase type 3) is the most extensively studied enzyme in persistent pulmonary hypertension of the newborn ( ... The NO then mediates pulmonary vasodilation via cyclic guanosine monophosphate (cGMP). Cyclic adenosine monophosphate (cAMP) is ...
In this, effects of fast zinc flux, taking place within a few seconds to minutes will be distinguish from slower types of zinc ... Key signaling pathways will be described in detail for the different cell types of the immune system. ... and phosphodiesterases, will be highlighted in this article. In addition, the interplay of zinc homeostasis and the redox ... Von Bülow, V.; Rink, L.; Haase, H. Zinc-mediated inhibition of cyclic nucleotide phosphodiesterase activity and expression ...
cyclic-nucleotide phosphodiesterase activity. 0.00138160435598277. GO:0008599. protein phosphatase type 1 regulator activity. ... cyclic-nucleotide phosphodiesterase activity. 0.00123283964400915. GO:0014821. phasic smooth muscle contraction. ... cyclic-nucleotide-mediated signaling. 0.000108706869078756. GO:0007200. G-protein signaling, coupled to IP3 second messenger ( ... G-protein signaling, coupled to cyclic nucleotide second messenger. 0.000861503214965366. GO:0021826. substrate-independent ...
The roles of cyclic nucleotide phosphodiesterases (PDEs) in steroidogenesis. Curr Opin Pharmacol (2011) 11(6):670-5. doi: ... A key issue is the connection of CHOL levels in the LE/LY to the homeostasis of CHOL synthesis in the ER (100). Three types of ... Studying mechanisms of cAMP and cyclic nucleotide phosphodiesterase signaling in Leydig cell function with phosphoproteomics. ... Phosphodiesterases and adrenal Cushing in mice and humans. Horm Metab Res (2014) 46(12):863-8. doi: 10.1055/s-0034-1389916 ...
PDEase_I; 35-cyclic nucleotide phosphodiesterase. pfam08629. Location:1 → 47. PDE8; PDE8 phosphodiesterase. pfam13426. ... Gene type. protein coding. RefSeq status. REVIEWED. Organism. Homo sapiens Lineage. Eukaryota; Metazoa; Chordata; Craniata; ... PDEase_I; 35-cyclic nucleotide phosphodiesterase. pfam08629. Location:1 → 47. PDE8; PDE8 phosphodiesterase. pfam13426. ... PDE8; PDE8 phosphodiesterase. pfam00233. Location:613 → 860. PDEase_I; 35-cyclic nucleotide phosphodiesterase. pfam13426. ...
Second, Orn is a key enzyme in bacterial cyclic-di-GMP (c-di-GMP) signaling. The nucleotide second messenger c-di-GMP is ... Degradation of 32P-GG (A) and 32P-AAAAAGG (B) by whole cell lysates of wild-type, orn mutant, orn mutant complemented with orn ... P. aeruginosa ∆orn accumulates pGpG that in turn inhibits c-di-GMP-specific phosphodiesterases (Cohen et al., 2015; Orr et al ... 2013) Cyclic di-GMP: the first 25 years of a universal bacterial second messenger Microbiology and Molecular Biology Reviews 77 ...
Cyclic nucleotide-binding domain, Crp-like helix-turn-helix domain [Interproscan].","protein_coding" "AAC74608","dgcZ"," ... ","DNA polymerase III PolC-type (PolIII) [Ensembl]. DNA polymerase III polC-type N-terminus I, DNA polymerase III polC-type N- ... ","phosphodiesterase activity on bis-pNPP [Ensembl]. Calcineurin-like phosphoesterase superfamily domain [Interproscan]."," ... "cyclic nucleotide-binding domain protein [Ensembl].","protein_coding" "AKI48746","L2625_00816","Listeria monocytogenes","RarD ...
Mark Type III cGMP-inhibited cyclic nucleotide phosphodiesterases (PDE3 gene family) Manganiello, Vincent C ; Taira, Masato ; ... Mark Diversity in cyclic nucleotide phosphodiesterase isoenzyme families Manganiello, Vincent C ; Murata, Taku ; Taira, Masato ... Mark Protein kinase A-dependent activation of PDE4 (cAMP-specific cyclic nucleotide phosphodiesterase) in cultured bovine ... Mark Phosphorylation and activation of hormone-sensitive adipocyte phosphodiesterase type 3B Degerman, Eva LU ; Landström, Tova ...
Expression and regulation of cyclic nucleotide phosphodiesterases in human and rat pancreatic islets. ... Genetic predisposition for beta cell fragility underlies type 1 and type 2 diabetes. Nat Genet. 2016 May;48(5):519-27 ... Reinbothe TM, Alkayyali S, Ahlqvist E, Tuomi T, Isomaa B, Lyssenko V, Renström E. The human L-type calcium channel Ca(v)1.3 ... Dayeh TA, Olsson AH, Volkov P, Almgren P, Rönn T, Ling C. Identification of CpG-SNPs associated with type 2 diabetes and ...
A host type I interferon response is induced by cytosolic sensing of the bacterial second messenger cyclic-di-GMP. J Exp Med. ... Single nucleotide polymorphisms of human STING can affect innate immune response to cyclic dinucleotides. PLoS One. 2013;8(10): ... dithio-substituted diastereomer CDNs were resistant to digestion with phosphodiesterase, stimulated higher expression of IFN-β ... Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science. 2013;339(6121):786-791 ...
35-cyclic nucleotide phosphodiesterase. 0.03. OrthoFinder. lcl,BLLF01000497.1_cds_GFH12377.1_6854. HaLaN_08048, GFH12377. 35 ... Type. GO Term. Name. Evidence. Source. MF. GO:0000166. nucleotide binding. IEP. Enrichment. ... GAF domain; 35-cyclic nucleotide phosphodiesterase,.... 0.01. OrthoFinder. lcl,BLLF01000266.1_cds_GFH09823.1_4300. HaLaN_ ... cyclic-nucleotide phosphodiesterase activity. None. Extended. MF. GO:0004114. 3,5-cyclic-nucleotide phosphodiesterase ...
This cyclic nucleotide relaxes the smooth muscles in the penile arteries, allowing increased blood flow to the erectile tissues ... The primary class of medications for ED includes phosphodiesterase type 5 (PDE5) inhibitors, such as sildenafil (Viagra), ... What Are the Different Types of Opioids Medicine?. Opioids are a class of drugs derived from opium poppies or synthesised to ... These medications function by inhibiting the action of PDE5, an enzyme that breaks down cyclic guanosine monophosphate (cGMP). ...
Type 3 Cyclic Nucleotide Phosphodiesterases 100% * Adipocytes 62% * Type 2 Diabetes Mellitus 49% ... Cyclic Nucleotide Phosphodiesterase 3 Signaling Complexes. Ahmad, F., Degerman, E. & Manganiello, V. C., 2012, In: Hormone and ... Second messengers , Cyclic nucleotide phosphodiesterases. Manganiello, V. C. & Degerman, E., 2021 Jul 29, Encyclopedia of ... Cyclic Nucleotide Phosphodiesterases: important signaling modulators and therapeutic targets. Ahmad, F., Murata, T., Shimizu, K ...
Cyclic nucleotide turnover/signalling C *Adenylyl cyclases (ACs) C. *Cyclic GMP-AMP synthase ... Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family C. *Type IV RTKs: VEGF (vascular endothelial growth factor) receptor ... Exchange proteins activated by cyclic AMP (EPACs) C. *Phosphodiesterases, 3,5-cyclic nucleotide (PDEs) C ... Type I PIP kinases (1-phosphatidylinositol-4-phosphate 5-kinase family). *Type II PIP kinases (1-phosphatidylinositol-5- ...
Cyclic Nucleotide Phosphodiesterases, Type 1. *Cyclic Nucleotide Phosphodiesterases, Type 2. *Cyclic Nucleotide ... Cyclic-GMP Phosphodiesterases" by people in Profiles.. * The effect of vardenafil, a potent and highly selective ... Cyclic-GMP Phosphodiesterases" by people in this website by year, and whether "3,5-Cyclic-GMP Phosphodiesterases" was a major ... Cyclic-GMP Phosphodiesterases" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH ( ...
cGMP (Cyclic guanosine monophosphate is a cyclic nucleotide derived from guanosine triphosphate (GTP)).. ... from the phosphodiesterase class).. PDE5 inhibitors (A phosphodiesterase type 5 inhibitor is a drug used to block the ... PDE5 (cGMP specific phosphodiesterase type 5 is an enzyme (EC 3.1.4.17) ... degradative action of phosphodiesterase type 5 on cyclic GMP in the smooth muscle cells lining the blood vessels supplying the ...
... as well as antibodies to the myelin-specific cyclic nucleotide phosphodiesterase (CNP). These authors did not look at stages ... Type-1 astrocytes, the other major macroglial cell type in the optic nerve, do not appear to express either PDGF-αR or PDGF-βR ... possibly type-1 astrocytes (Richardson et al., 1988; Pringle et al., 1989; Yeh et al., 1991). Either of these cell types might ... type-l-like) astrocytes (see Materials and methods for details). These different glial cell types were maintained for 24 hours ...
... mice heterozygous for the oligodendrocyte gene cyclic nucleotide phosphodiesterase (Cnp1) on a BL/6 background were studied;. a ... Instead they showed novel concept-type specific response patterns. The absence of the classic ERP components suggests that CT- ... These findings further highlight the critical role that expertise and type of experience have on olfactory functions. ... Electrophysiological correlates of concept type shifts. PLoS One, 14(3): e0212624. doi:10.1371/journal.pone.0212624. ...
Cyclic-Nucleotide Phosphodiesterase. 3,5-Cyclic-AMP Phosphodiesterases. Acetylserotonin N-Methyltransferase. Acetylserotonin ... Unpublished Works [Publication Type]. Unpublished Works. V03 - Study Characteristics. Case Reports [Publication Type]. Case ... Published Erratum [Publication Type]. Published Erratum. Retraction of Publication [Publication Type]. Retraction of ... Multicenter Study [Publication Type]. Multicenter Study. Randomized Controlled Trial [Publication Type]. Randomized Controlled ...
  • PDEs are a diverse family of enzymes that have different tissue distributions and functions but that all exert their effect by lowering intracellular levels of cyclic nucleotides, such as cyclic guanosine monophosphate (cGMP). (medscape.com)
  • These medications function by inhibiting the action of PDE5, an enzyme that breaks down cyclic guanosine monophosphate (cGMP). (nonstoptraffic.org)
  • In mammals, 19 different genes encode the cyclic nucleotide phosphodiesterases (PDEs), the enzymes that hydrolyze and inactivate cAMP and cGMP. (nih.gov)
  • PDE5 (cGMP specific phosphodiesterase type 5 is an enzyme (EC 3.1.4.17) from the phosphodiesterase class). (buy-free-ship.com)
  • This complex in turn activates cGMP-phosphodiesterase which rapidly hydrolyzes cytosolic cGMP. (nii.ac.jp)
  • 2) Biochemical analyses revealed that -subunit of transducin consists of two components which are different in GTP-binding activity (T.Akino), that the Km value of cGMP-phosphodiesterase increases about 10-fold in the light (M.Murakami), and that phosphatidyl-inositol turnover mediated by a GTP-binding protein was activated by light (T.Amakawa). (nii.ac.jp)
  • Phosphodiesterase type 5 (PDE5) inhibitors are the principal oral agents used in ED. (medscape.com)
  • The primary class of medications for ED includes phosphodiesterase type 5 (PDE5) inhibitors, such as sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra). (nonstoptraffic.org)
  • PDE5 inhibitors (A phosphodiesterase type 5 inhibitor is a drug used to block the degradative action of phosphodiesterase type 5 on cyclic GMP in the smooth muscle cells lining the blood vessels supplying the corpus cavernosum of the penis). (buy-free-ship.com)
  • Erectile dysfunction can be treated in 95% of cases by the intake of the drugs from the group of phosphodiesterase type 5 inhibitors (PDE-5). (genericsbot.com)
  • Currently, the first-line drugs for the treatment of ED are phosphodiesterase type 5 inhibitors (PDE-5). (genericsbot.com)
  • The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE1 subfamily. (thermofisher.com)
  • The protein encoded by this gene is a cyclic nucleotide phosphodiesterase (PDE) that catalyzes the hydrolysis of the second messenger cAMP. (nih.gov)
  • Recent progress in the field of cyclic nucleotides has shown that a large array of closely related proteins is involved in each step of the signal transduction cascade. (nih.gov)
  • Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1C is an enzyme that in humans is encoded by the PDE1C gene. (wikipedia.org)
  • Second, Orn is a key enzyme in bacterial cyclic-di-GMP (c-di-GMP) signaling. (elifesciences.org)
  • potentially interfering with co-factor or co-enzyme binding) or of mixed type. (guidetopharmacology.org)
  • The effect of vardenafil, a potent and highly selective phosphodiesterase-5 inhibitor for the treatment of erectile dysfunction, on the cardiovascular response to exercise in patients with coronary artery disease. (ouhsc.edu)
  • Genetic association study of phosphodiesterase 8B gene with subclinical hypothyroidism in pregnant women. (nih.gov)
  • Frequency and effect on serum TSH of phosphodiesterase 8B (PDE8B) gene polymorphisms in patients with sporadic nonautoimmune subclinical hypothyroidism. (nih.gov)
  • RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in HFpEF) was a multicenter randomized trial testing the impact of sildenafil on peak VO2 in stable outpatients with chronic HFpEF. (elsevierpure.com)
  • The undesirable effect of drugs from the PDE-5 group is due to their inhibition of not only phosphodiesterase type 5, but also other types of PDE, which causes their effect on the nervous, cardiovascular and respiratory system, as well as visual organs and mucous membrane. (genericsbot.com)
  • Binding of ligands to PRRs activates adaptor molecules and downstream signaling events, leading to the secretion of type I IFNs, inflammatory cytokines, chemokines, and antimicrobial peptides. (jci.org)
  • Enzymes that catalyze the hydrolysis of cyclic GMP to yield guanosine-5'-phosphate. (ouhsc.edu)
  • 3',5'-Cyclic-GMP Phosphodiesterases" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (ouhsc.edu)
  • A comparable heterogeneity has been discovered for the enzymes involved in the inactivation of cyclic nucleotide signaling. (nih.gov)
  • In γ-proteobacteria, 3-'5' exoribonucleases comprise up to eight distinct enzymes. (elifesciences.org)
  • Main underlying molecular mechanisms and targets affected by altered zinc homeostasis, including kinases, caspases, phosphatases, and phosphodiesterases, will be highlighted in this article. (mdpi.com)
  • Expression of phosphodiesterase-5 in lymphatic malformation tissue. (ucdenver.edu)
  • A Syntenic Cross Species Aneuploidy Genetic Screen Links RCAN1 Expression to β-Cell Mitochondrial Dysfunction in Type 2 Diabetes. (lu.se)
  • Across languages, ideophones stand out as marked words due to special phonotactics, expressive morphology including certain types of reduplication, and relative syntactic independence, in addition to production features like prosodic foregrounding and common co-occurrence with iconic gestures. (mpi.nl)
  • Consequently, the current state of mTBI care is restricted to advising patients to gradually return to full activity based on the progression of their symptoms [ 5 ]. (biomedcentral.com)
  • Signs and symptoms of TBRF include cyclic febrile episodes, nausea, and vomiting ( 1 ). (cdc.gov)
  • Cyclic nucleotide-binding domain, Crp-like helix-turn-helix domain [Interproscan]. (ntu.edu.sg)
  • To date, there are about a dozen drugs in the IPDE-5 group. (genericsbot.com)
  • Moreover, this dose is 5-10 times higher than the dose necessary to stimulate the caudate nucleus (extrapyramidal motor system) and the neural structures regulating the sleep-wake cycle, the 2 functions that are most sensitive to caffeine. (medscape.com)
  • Degradation of RNA polymers, an ubiquitous process in all cells, is catalyzed by specific subsets of endo- and exoribonucleases that together recycle RNA fragments into nucleotide monophosphate. (elifesciences.org)
  • The temporal and spatial distribution of PDGF- α R + cells, together with 125 I-PDGF binding studies on subsets of glial cells in vitro, suggests that PDGF- α R may be expressed predominantly, or exclusively, by cells of the oligodendrocyte-type-2 astrocyte (O-2A) lineage. (biologists.com)
  • Patients with AF had higher N-terminal pro-B-type natriuretic peptide, aldosterone, endothelin-1, troponin I, and C-telopeptide for type I collagen levels, suggesting more severe neurohumoral activation, myocyte necrosis, and fibrosis. (elsevierpure.com)
  • HBO treatment (100% oxygen at 2.5 atmospheres absolute, 60 min/day, 5 days/week) lasted for 5 weeks. (bvsalud.org)
  • Specifically, the increase in pGpG inhibits upstream phosphodiesterases that degrade c-di-GMP, thereby triggering phenotypes associated with high cellular c-di-GMP levels. (elifesciences.org)
  • The types of medications can be divided into oral, topical, injectable, and intraurethrally inserted. (medscape.com)
  • This cyclic nucleotide relaxes the smooth muscles in the penile arteries, allowing increased blood flow to the erectile tissues. (nonstoptraffic.org)
  • Evidence for a critical functional role for type I IFNs led to interrogation of candidate innate immune sensing pathways that might be triggered by tumor presence and induce type I IFN production. (jci.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. (ouhsc.edu)
  • The 2 major coffee types are arabica ( Coffea arabica ) and robusta ( Coffea canephora ). (medscape.com)
  • In genetical analysis, a retina-specific protein named MEKA was found, which affects the phosphodiesterase activity (N.Miki). (nii.ac.jp)