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 a class of molecules that contain a cyclic phosphate group and a nitrogenous base, and play important roles in cellular signaling pathways.
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
Purinones are a class of organic compounds derived from purines, which are important for the metabolism of nucleic acids and have potential therapeutic applications in the medical field.
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 contain the nitrogenous base adenine and are involved in various biological processes, including energy metabolism and DNA synthesis.
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 a type of nucleotide that contains the nitrogenous base guanine and play important roles in various biological processes, including DNA and RNA synthesis, energy metabolism, and signal transduction.
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 are a class of cyclic ethers that contain a ring of atoms with an oxygen atom bonded to two adjacent carbon atoms.
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.

Characterization of TbPDE2A, a novel cyclic nucleotide-specific phosphodiesterase from the protozoan parasite Trypanosoma brucei. (1/68)

This study reports the identification and characterization of a cAMP-specific phosphodiesterase from the parasitic hemoflagellate Trypanosoma brucei. TbPDE2A is a class I phosphodiesterase. Its catalytic domain exhibits 30-40% sequence identity with those of all 11 mammalian phosphodiesterase (PDE) families, as well as with PDE2 from Saccharomyces cerevisiae, dunce from Drosophila melanogaster, and regA from Dictyostelium discoideum. The overall structure of TbPDE2A resembles that of human PDE11A in that its N-terminal region contains a single GAF domain. This domain is very similar to those of the mammalian PDE2, -5, -6, -10, and -11, where it constitutes a potential cGMP binding site. TbPDE2A can be expressed in S. cerevisiae, and it complements an S. cerevisiae PDE deletion strain. Recombinant TbPDE2A is specific for cAMP, with a K(m) of approximately 2 micrometer. It is entirely resistant to the nonselective PDE inhibitor 3-isobutyl-1-methylxanthine, but it is sensitive to trequinsin, dipyridamole, sildenafil, and ethaverine with IC(50) values of 5.4, 5.9, 9.4, and 14.2 micrometer, respectively. All four compounds inhibit proliferation of bloodstream form trypanosomes in culture, indicating that TbPDE2A is an essential enzyme.  (+info)

Cyclic GMP regulation of the L-type Ca(2+) channel current in human atrial myocytes. (2/68)

1. The regulation of the L-type Ca(2+) current (I(Ca)) by intracellular cGMP was investigated in human atrial myocytes using the whole-cell patch-clamp technique. 2. Intracellular application of 0.5 microM cGMP produced a strong stimulation of basal I(Ca) (+64 +/- 5 %, n = 60), whereas a 10-fold higher cGMP concentration induced a 2-fold smaller increase (+36 +/- 8 %, n = 35). 3. The biphasic response of I(Ca) to cGMP was not mimicked by the cGMP-dependent protein kinase (PKG) activator 8-bromoguanosine 3',5' cyclic monophosphate (8-bromo-cGMP, 0.5 or 5 microM), and was not affected by the PKG inhibitor KT 5823 (100 nM). 4. In contrast, cGMP stimulation of I(Ca) was abolished by intracellular perfusion with PKI (10 microM), a selective inhibitor of the cAMP-dependent protein kinase (PKA). 5. Selective inhibition of the cGMP-inhibited phosphodiesterase (PDE3) by extracellular cilostamide (100 nM) strongly enhanced basal I(Ca) in control conditions (+78 +/- 13 %, n = 7) but had only a marginal effect in the presence of intracellular cGMP (+22 +/- 7 % in addition to 0.5 microM cGMP, n = 11; +20 +/- 22 % in addition to 5 microM cGMP, n = 7). 6. Application of erythro-9-[2-hydroxy-3-nonyl]adenine (EHNA, 30 microM), a selective inhibitor of the cGMP-stimulated phosphodiesterase (PDE2), fully reversed the secondary inhibitory effect of 5 microM cGMP on I(Ca) (+99 +/- 16 % stimulation, n = 7). 7. Altogether, these data indicate that intracellular cGMP regulates basal I(Ca) in human atrial myocytes in a similar manner to NO donors. The effect of cGMP involves modulation of the cAMP level and PKA activity via opposite actions of the nucleotide on PDE2 and PDE3.  (+info)

Local response of L-type Ca(2+) current to nitric oxide in frog ventricular myocytes. (3/68)

1. The regulation of L-type Ca(2+) current (I(Ca)) by the two nitric oxide (NO) donors sodium nitroprusside (SNP, 1 microM to 1 mM) and (+/-)-S-nitroso-N-acetylpenicillamine (SNAP, 3 or 10 microM) was investigated in frog ventricular myocytes using double voltage clamp and double-barrelled microperfusion techniques. 2. SNP and SNAP depressed the isoprenaline (ISO, 10-100 nM)- or forskolin (FSK, 1 microM)-mediated stimulation of I(Ca) via cGMP activation of the cGMP-stimulated phosphodiesterase (PDE2). Complete inhibition of the ISO (100 nM) response was observed at 1 mM SNP. 3. When SNP was applied locally, i.e. to one-half of the cell, and ISO to the whole cell, the response of I(Ca) to ISO was strongly antagonized in the cell half exposed to SNP (up to 100 % inhibition at 1 mM SNP) but a relatively small depression was observed in the other half of the cell (only 20 % inhibition at 1 mM SNP). 4. The NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (carboxy-PTIO, 1 mM) reversed the local effect of SNAP (3 microM) on FSK-stimulated I(Ca) when applied to the same side as the NO donor, but had no effect when applied to the other side of the cell. 5. A local application of erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA, 30 microM), a selective inhibitor of PDE2, fully reversed the local effect of SNP (100 microM) or SNAP (10 microM) on I(Ca) but had no effect on the distant response. 6. When EHNA was applied on the distant side, with SNP (1 mM) and ISO (100 nM) applied locally, the distant effect of SNP was fully reversed. 7. Our results demonstrate that in frog ventricular myocytes stimulation of guanylyl cyclase by NO leads to a strong local depletion of cAMP near the L-type Ca(2+) channels due to activation of PDE2, but only to a modest reduction of cAMP in the rest of the cell. This may be explained by the existence of a tight microdomain between L-type Ca(2+) channels and PDE2.  (+info)

NO-cGMP pathway increases the hyperpolarisation-activated current, I(f), and heart rate during adrenergic stimulation. (4/68)

OBJECTIVES: The role of the nitric oxide (NO)-cGMP pathway in the autonomic modulation of cardiac pacemaking is controversial and may involve an interplay between the L-type calcium current, I(CaL), and the hyperpolarisation activated current, I(f). We tested the hypothesis that following adrenergic stimulation, the NO-cGMP pathway stimulates phosphodiesterase 2 (PDE2) to reduce cAMP dependent stimulation of I(f) and heart rate (HR). METHODS: In the presence of norepinephrine (NE, 1 microM), the effects of the NO donor sodium nitroprusside (SNP) were evaluated in sinoatrial node (SAN)/atria preparations and isolated SAN cells from adult guinea pigs. RESULTS: Contrary to our hypothesis, SNP (10 and 100 microM, n=5) or the membrane permeable cGMP analogue, 8Br-cGMP (0.5 mM, n=6) transiently increased HR by 5+/-1, 12+/-1 and 12+/-2 beats/min, respectively. The guanylyl cyclase inhibitor 1H-(1,2,4)-oxadiazolo-(4,3-a)-quinoxalin-1-one (ODQ, 10 microM, n=5) abolished the increase in HR to SNP (100 microM) as did the I(f) blockers caesium chloride (2 mM, n=7) and 4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino)-pyrimidinium chloride (ZD7288, 1 microM, n=7). Addition of SNP (10 microM) also transiently increased I(f) in SAN cells (n=5). After inhibition of PDE2 with erythro-9-(2-hydroxy-3-nonyl)-adenine (EHNA, 10 microM, n=5), the increase in HR to SNP in the presence of NE was significantly augmented and maintained. RT-PCR analysis confirmed the presence of PDE2 in addition to cGMP inhibited PDE3 mRNA in central SAN tissue. CONCLUSIONS: These results suggest that during adrenergic stimulation, activation of the NO-cGMP pathway does not decrease HR, but has a transient stimulatory effect that is I(f) dependent, and is limited in magnitude and duration by stimulation of PDE2.  (+info)

The cAMP-specific phosphodiesterase TbPDE2C is an essential enzyme in bloodstream form Trypanosoma brucei. (5/68)

Chemotherapy of human sleeping sickness, a fatal disease caused by the protozoan parasite Trypanosoma brucei, is in a dismal state, and the identification and characterization of new drug targets is an urgent prerequisite for an improvement of the dramatic situation in the field. Over the last several years, inhibitors of cyclic nucleotide-specific phosphodiesterases have proven to be highly successful drug candidates for an assortment of clinical conditions. Their potential as antiparasitic drugs has not been explored so far. This study reports the characterization of a cAMP-specific phosphodiesterase from T. brucei, TbPDE2C. This enzyme is a class I phosphodiesterase, and it is a member of a small enzyme family in T. brucei, TbPDE2. Inhibitors of this enzyme block the proliferation of bloodstream form trypanosomes in culture. RNA interference experiments demonstrated that the TbPDE2 family, and in particular TbPDE2C, are essential for maintaining intracellular cAMP concentrations within a physiological range. Bloodstream form trypanosomes are exquisitely sensitive to elevated concentrations of intracellular cAMP, and a disruption of TbPDE2C function quickly leads to the disruption of nuclear and cellular cell division, and to cell death. TbPDE2C might represent a novel drug target for the development of new and effective trypanocidal drugs.  (+info)

Cloning and characterization of a cAMP-specific phosphodiesterase (TbPDE2B) from Trypanosoma brucei. (6/68)

Here we report the cloning, expression, and characterization of a cAMP-specific phosphodiesterase (PDE) from Trypanosoma brucei (TbPDE2B). Using a bioinformatic approach, two different expressed sequence tag clones were identified and used to isolate the complete sequence of two identical PDE genes arranged in tandem. Each gene consists of 2,793 bases that predict a protein of 930 aa with a molecular mass of 103.2 kDa. Two GAF (for cGMP binding and stimulated PDEs, Anabaena adenylyl cyclases, and Escherichia coli FhlA) domains, similar to those contained in many signaling molecules including mammalian PDE2, PDE5, PDE6, PDE10, and PDE11, were located N-terminal to a consensus PDE catalytic domain. The catalytic domain is homologous to the catalytic domain of all 11 mammalian PDEs, the Dictyostelium discoideum RegA, and a probable PDE from Caenorhabditis elegans. It is most similar to the T. brucei PDE2A (89% identity). TbPDE2B has substrate specificity for cAMP with a K(m) of 2.4 microM. cGMP is not hydrolyzed by TbPDE2B nor does this cyclic nucleotide modulate cAMP PDE activity. The nonselective PDE inhibitors 3-isobutyl-1-methylxanthine, papaverine and pentoxifyline are poor inhibitors of TbPDE2B. Similarly, PDE inhibitors selective for the mammalian PDE families 2, 3, 5, and 6 (erythro-9-[3-(2-hydroxynonyl)]-adenine, enoximone, zaprinast, and sildenafil) were also unable to inhibit this enzyme. However, dipyridamole was a reasonably good inhibitor of this enzyme with an IC50 of 27 microM. cAMP plays key roles in cell growth and differentiation in this parasite, and PDEs are responsible for the hydrolysis of this important second messenger. Therefore, parasite PDEs, including this one, have the potential to be attractive targets for selective drug design.  (+info)

Hydrolysis of N-methyl-D-aspartate receptor-stimulated cAMP and cGMP by PDE4 and PDE2 phosphodiesterases in primary neuronal cultures of rat cerebral cortex and hippocampus. (7/68)

Stimulation of N-methyl-D-aspartate (NMDA) receptors on neurons activates both cAMP and cGMP signaling pathways. Experiments were carried out to determine which phosphodiesterase (PDE) families are involved in the hydrolysis of the cyclic nucleotides formed via this mechanism, using primary neuronal cultures prepared from rat cerebral cortex and hippocampus. The nonselective PDE inhibitor 3-isobutyl-1-methylxanthine (IBMX) potentiated the ability of NMDA to increase cAMP and cGMP. However, among the family-selective inhibitors, only the PDE4 inhibitor rolipram enhanced the ability of NMDA to increase cAMP in the neurons. In contrast, only the PDE2 inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) enhanced the ability of NMDA to increase cGMP. Neither adenosine nor an adenosine deaminase inhibitor mimicked the effect of EHNA; this suggests that EHNA's inhibition of PDE2, not its effects on adenosine metabolism, mediates its effects on NMDA-stimulated cGMP concentrations. The PDE inhibitor-augmented effects of NMDA on cAMP and cGMP formation were antagonized by 5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine maleate (MK-801), verifying NMDA receptor mediation. In contrast, only NMDA-mediated cGMP formation was affected by altering either nitric oxide signaling or guanylyl cyclase; this suggests that NMDA-induced changes in cAMP are not secondary to altered cGMP concentrations. Overall, the present findings indicate that cAMP and cGMP formed in neurons as a result of NMDA receptor stimulation are hydrolyzed by PDE4 and PDE2, respectively. Selective inhibitors of the two PDE families will differentially affect the functional consequences of activation of these two signaling pathways by NMDA receptor stimulation.  (+info)

Attenuation of cAMP accumulation in adult rat cardiac fibroblasts by IL-1beta and NO: role of cGMP-stimulated PDE2. (8/68)

Treatment of cultured adult rat cardiac fibroblasts with interleukin-1beta (IL-1beta) induces the inducible nitric oxide synthase (iNOS) expression, increases nitric oxide (NO) and cGMP production, and attenuates cAMP accumulation in response to isoproterenol by ~50%. Reduced cAMP accumulation is due to NO production: the effect is mimicked by NO donors and prevented by N(G)-monomethyl-L-arginine, an NOS inhibitor. Effects of NO are not restricted to the beta-adrenergic response; the response to forskolin is similarly diminished. NO donors only slightly (12%) decrease forskolin-stimulated adenylyl cyclase (AC) activity in cardiac fibroblast plasma membranes, suggesting that the main effect of NO is not a direct one on AC. An inhibitor of soluble guanylyl cyclase inhibits the effects of IL-1beta and NO donors; inhibition of cGMP-dependent protein kinase is without effect. 3-Isobutyl-1-methylxanthine, a nonspecific phosphodiesterase (PDE) inhibitor, and erythro-9-(2-hydroxy-3-nonyl)adenine, a specific inhibitor of the cGMP-stimulated PDE (PDE2), completely restore cAMP accumulation in sodium nitroprusside-treated fibroblasts and largely reverse the attenuated response in IL-1beta-treated fibroblasts. Although NO reportedly acts by reducing AC activity in some cells, in cardiac fibroblasts NO production decreases cAMP accumulation largely by the cGMP-mediated activation of PDE2.  (+info)

Cyclic Nucleotide Phosphodiesterases, Type 1 (PDE1) are a family of enzymes that break down cyclic nucleotides, such as cyclic AMP (cAMP) and cyclic GMP (cGMP), into their corresponding monophosphates. These enzymes play a crucial role in regulating various cellular processes, including muscle contraction, neurotransmission, and immune function. In the medical field, PDE1 inhibitors are being investigated as potential treatments for a variety of conditions, including heart failure, erectile dysfunction, and neurological disorders. These inhibitors work by increasing the levels of cAMP or cGMP in the cell, leading to the activation of downstream signaling pathways that promote beneficial effects. However, PDE1 inhibitors can also have side effects, such as headache, flushing, and gastrointestinal symptoms, and their use may be limited by potential drug interactions and other safety concerns. Therefore, further research is needed to fully understand the therapeutic potential and safety profile of PDE1 inhibitors in the medical field.

3',5'-Cyclic-AMP phosphodiesterases (PDEs) are a family of enzymes that play a crucial role in regulating the levels of cyclic AMP (cAMP) in the body. cAMP is a signaling molecule that is involved in a wide range of cellular processes, including cell growth, differentiation, and metabolism. PDEs are responsible for breaking down cAMP into inactive products, thereby regulating the levels of this signaling molecule in the body. There are 11 different subtypes of PDEs, each with its own specific substrate specificity and tissue distribution. In the medical field, PDEs are of particular interest because they are involved in the regulation of many different physiological processes, including the cardiovascular system, the nervous system, and the immune system. In addition, PDEs are the targets of many drugs, including some used to treat conditions such as erectile dysfunction, asthma, and heart failure.

Cyclic Nucleotide Phosphodiesterases, Type 4 (PDE4) are a family of enzymes that break down cyclic AMP (cAMP) and cyclic GMP (cGMP) in the body. These enzymes play a crucial role in regulating various cellular processes, including inflammation, immune response, and muscle contraction. PDE4 enzymes are found in a variety of tissues, including the lungs, heart, and immune cells. They are also present in the brain, where they play a role in regulating mood and cognition. In the medical field, PDE4 inhibitors are used to treat a variety of conditions, including asthma, chronic obstructive pulmonary disease (COPD), psoriasis, and depression. These drugs work by inhibiting the activity of PDE4 enzymes, leading to an accumulation of cAMP and cGMP in the cell. This, in turn, can result in a range of therapeutic effects, depending on the tissue and condition being treated.

Cyclic Nucleotide Phosphodiesterases, Type 3 (PDE3) are a family of enzymes that play a crucial role in regulating the levels of cyclic AMP (cAMP) and cyclic GMP (cGMP) in the body. These enzymes are found in a variety of tissues, including the heart, blood vessels, and immune system. PDE3 enzymes are responsible for breaking down cAMP and cGMP, which are important signaling molecules that regulate a wide range of cellular processes, including muscle contraction, blood vessel dilation, and immune cell activation. By breaking down these molecules, PDE3 enzymes help to maintain the appropriate balance of cAMP and cGMP in the body. In the medical field, PDE3 inhibitors are often used to treat conditions such as heart failure, high blood pressure, and asthma. These drugs work by blocking the activity of PDE3 enzymes, which leads to increased levels of cAMP and cGMP in the body. This, in turn, can help to improve blood flow, relax blood vessels, and reduce inflammation, among other effects. Overall, PDE3 enzymes play a critical role in regulating the levels of cAMP and cGMP in the body, and PDE3 inhibitors are an important class of drugs used to treat a variety of medical conditions.

Cyclic Nucleotide Phosphodiesterases, Type 2 (PDE2) are a family of enzymes that break down cyclic nucleotides, such as cyclic AMP (cAMP) and cyclic GMP (cGMP), into their corresponding monophosphates. These enzymes play a crucial role in regulating various cellular processes, including signal transduction, gene expression, and metabolism. In the medical field, PDE2 inhibitors are being investigated as potential therapeutic agents for a variety of diseases, including Parkinson's disease, Alzheimer's disease, and schizophrenia. These inhibitors work by increasing the levels of cAMP and cGMP in the cell, which can lead to the activation of downstream signaling pathways and the modulation of various cellular processes. PDE2 inhibitors have also been shown to have anti-inflammatory and anti-cancer effects, and are being studied as potential treatments for inflammatory diseases and cancer. However, more research is needed to fully understand the therapeutic potential of PDE2 inhibitors and to develop safe and effective drugs for these indications.

Phosphoric diester hydrolases are a group of enzymes that catalyze the hydrolysis of phosphoric diesters, which are esters of phosphoric acid. These enzymes are involved in a variety of biological processes, including the breakdown of nucleic acids, the metabolism of lipids, and the regulation of signaling pathways. In the medical field, phosphoric diester hydrolases are important for the proper functioning of the body. For example, they are involved in the breakdown of nucleic acids, which are the building blocks of DNA and RNA. This process is essential for the replication and repair of DNA, as well as the production of proteins from genetic information. Phosphoric diester hydrolases are also involved in the metabolism of lipids, which are a type of fat that is stored in the body. These enzymes help to break down lipids into smaller molecules that can be used for energy or stored for later use. In addition, phosphoric diester hydrolases play a role in the regulation of signaling pathways, which are the communication networks that allow cells to respond to changes in their environment. These enzymes help to control the activity of signaling molecules, which can affect a wide range of cellular processes, including cell growth, differentiation, and death. Overall, phosphoric diester hydrolases are important enzymes that play a variety of roles in the body. They are involved in the breakdown of nucleic acids, the metabolism of lipids, and the regulation of signaling pathways, and are essential for the proper functioning of the body.

2',3'-Cyclic-Nucleotide Phosphodiesterases (CNP) are a family of enzymes that play a crucial role in regulating the levels of cyclic nucleotides, such as cyclic AMP (cAMP) and cyclic GMP (cGMP), in the body. These enzymes are responsible for breaking down cyclic nucleotides into their corresponding monophosphates, which are then further degraded into inorganic phosphate and ribose or guanine. Cyclic nucleotides are important signaling molecules that regulate a wide range of cellular processes, including gene expression, cell growth and differentiation, and ion channel activity. CNP enzymes are involved in the regulation of these processes by controlling the levels of cyclic nucleotides in the cell. There are several different types of CNP enzymes, including 2',3'-Cyclic-Nucleotide 3'-Phosphodiesterase (CNP), 2',3'-Cyclic-Nucleotide 5'-Phosphodiesterase (CNPB), and 2',3'-Cyclic-Nucleotide 5'-Phosphodiesterase (CNPA). These enzymes are found in a variety of tissues and cells throughout the body, including the brain, heart, and immune system. Abnormalities in the function of CNP enzymes have been linked to a number of diseases and disorders, including hypertension, heart failure, and certain types of cancer. As such, CNP enzymes are an important area of research in the field of medicine, with potential therapeutic applications in the treatment of these conditions.

In the medical field, "Nucleotides, Cyclic" refers to a class of molecules that are composed of a cyclic structure containing a nitrogenous base, a pentose sugar, and a phosphate group. These molecules are important components of DNA and RNA, which are the genetic material of all living organisms. Cyclic nucleotides are a subclass of nucleotides that have a cyclic structure formed by the condensation of the sugar and phosphate groups. They are involved in various cellular signaling pathways and have been implicated in the regulation of a wide range of physiological processes, including blood pressure, heart rate, and immune function. Examples of cyclic nucleotides include cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). These molecules are synthesized from their respective nucleoside triphosphates (ATP and GTP) by the action of enzymes called adenylate cyclase and guanylate cyclase, respectively.

3',5'-Cyclic-GMP Phosphodiesterases (cGMP-PDEs) are a family of enzymes that play a crucial role in regulating the levels of cyclic guanosine monophosphate (cGMP) in the body. cGMP is a second messenger molecule that is involved in a wide range of cellular processes, including smooth muscle relaxation, neurotransmission, and immune cell function. cGMP-PDEs are responsible for breaking down cGMP into guanosine monophosphate (GMP), thereby terminating the signaling effects of cGMP. There are 11 different subtypes of cGMP-PDEs, each with different tissue distribution and substrate specificity. In the medical field, cGMP-PDEs are of particular interest because they are targeted by a class of drugs called phosphodiesterase inhibitors (PDE inhibitors). PDE inhibitors are used to treat a variety of conditions, including erectile dysfunction, pulmonary hypertension, and glaucoma. By inhibiting cGMP-PDEs, PDE inhibitors increase the levels of cGMP in the body, leading to the desired therapeutic effects.

Cyclic Nucleotide Phosphodiesterases, Type 5 (PDE5) are a group of enzymes that break down cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) in the body. These enzymes play a crucial role in regulating various physiological processes, including blood flow, smooth muscle contraction, and neurotransmission. In the context of sexual function, PDE5 inhibitors are a class of drugs that work by blocking the action of PDE5, thereby increasing levels of cGMP in the penis. This leads to improved blood flow to the penis and helps to achieve and maintain an erection during sexual activity. PDE5 inhibitors are commonly used to treat erectile dysfunction (ED) and are also being studied for other conditions, such as pulmonary hypertension and vision loss.

Cyclic GMP (cGMP) is a signaling molecule that plays a crucial role in regulating various physiological processes in the body, including smooth muscle contraction, neurotransmission, and blood pressure regulation. It is synthesized from guanosine triphosphate (GTP) by the enzyme guanylate cyclase and is degraded by the enzyme phosphodiesterase. In the medical field, cGMP is often studied in the context of its role in the regulation of blood vessels and the cardiovascular system. For example, cGMP is involved in the dilation of blood vessels, which helps to lower blood pressure and improve blood flow. It is also involved in the regulation of heart rate and contractility. Abnormal levels of cGMP can lead to a variety of medical conditions, including hypertension, heart failure, and erectile dysfunction. In these cases, medications that either increase or decrease cGMP levels may be used to treat the underlying condition.

Cyclic Nucleotide Phosphodiesterases, Type 7 (PDE7) are a family of enzymes that break down cyclic nucleotides, such as cyclic AMP (cAMP) and cyclic GMP (cGMP), in the body. These enzymes play a crucial role in regulating various cellular processes, including cell growth, differentiation, and apoptosis. In the medical field, PDE7 inhibitors are being studied as potential therapeutic agents for a variety of diseases, including cancer, inflammatory disorders, and neurological disorders. These inhibitors work by blocking the activity of PDE7 enzymes, leading to an accumulation of cyclic nucleotides in the cell and activation of downstream signaling pathways. PDE7 inhibitors have shown promise in preclinical studies for the treatment of various types of cancer, including breast cancer, prostate cancer, and lung cancer. They have also been shown to have anti-inflammatory effects and may have potential as treatments for inflammatory disorders such as psoriasis and rheumatoid arthritis. Additionally, PDE7 inhibitors have been shown to have neuroprotective effects and may have potential as treatments for neurological disorders such as Alzheimer's disease and Parkinson's disease.

Cyclic AMP (cAMP) is a signaling molecule that plays a crucial role in many cellular processes, including metabolism, gene expression, and cell proliferation. It is synthesized from adenosine triphosphate (ATP) by the enzyme adenylyl cyclase, and its levels are regulated by various hormones and neurotransmitters. In the medical field, cAMP is often studied in the context of its role in regulating cellular signaling pathways. For example, cAMP is involved in the regulation of the immune system, where it helps to activate immune cells and promote inflammation. It is also involved in the regulation of the cardiovascular system, where it helps to regulate heart rate and blood pressure. In addition, cAMP is often used as a tool in research to study cellular signaling pathways. For example, it is commonly used to activate or inhibit specific signaling pathways in cells, allowing researchers to study the effects of these pathways on cellular function.

Rolipram is a medication that belongs to a class of drugs called phosphodiesterase type 4 (PDE4) inhibitors. It is primarily used to treat asthma and chronic obstructive pulmonary disease (COPD) by relaxing the muscles in the airways and improving breathing. Rolipram may also be used to treat other conditions, such as psoriasis and inflammatory bowel disease, by reducing inflammation in the body. It is usually taken by mouth in the form of tablets or capsules.

1-Methyl-3-isobutylxanthine, also known as IBMX, is a chemical compound that belongs to the xanthine family. It is a selective inhibitor of the enzyme phosphodiesterase type 4 (PDE4), which is involved in the breakdown of cyclic AMP (cAMP) in cells. In the medical field, IBMX is used as a research tool to study the effects of PDE4 inhibition on various physiological processes, including inflammation, pain, and airway smooth muscle contraction. It has also been investigated as a potential treatment for a variety of conditions, including asthma, chronic obstructive pulmonary disease (COPD), and psoriasis. However, IBMX is not currently approved for use as a therapeutic agent in humans, as it can have significant side effects, including nausea, vomiting, diarrhea, and increased heart rate. Additionally, prolonged use of IBMX can lead to the development of tolerance and dependence.

Purinones are a class of organic compounds that are derived from purine, a nitrogen-containing heterocyclic base found in nucleic acids such as DNA and RNA. Purinones are important in the field of medicine because they are involved in various biological processes, including energy metabolism, cell signaling, and immune function. One of the most well-known purinones is adenosine, which is a signaling molecule that plays a role in regulating blood flow, inflammation, and neurotransmission. Adenosine is also a precursor to ATP, the primary energy currency of cells. Other purinones include hypoxanthine, xanthine, and uric acid, which are involved in the metabolism of purines and the production of uric acid, a waste product that is excreted by the kidneys. High levels of uric acid in the blood can lead to gout, a painful joint condition. Purinones are also used in the development of drugs for a variety of medical conditions, including cancer, cardiovascular disease, and inflammatory disorders. For example, the drug allopurinol is used to lower uric acid levels in people with gout, while the drug caffeine is a purine derivative that is used to stimulate the central nervous system.

In the medical field, isoenzymes refer to different forms of enzymes that have the same chemical structure and catalytic activity, but differ in their amino acid sequence. These differences can arise due to genetic variations or post-translational modifications, such as phosphorylation or glycosylation. Isoenzymes are often used in medical diagnosis and treatment because they can provide information about the function and health of specific organs or tissues. For example, the presence of certain isoenzymes in the blood can indicate liver or kidney disease, while changes in the levels of specific isoenzymes in the brain can be indicative of neurological disorders. In addition, isoenzymes can be used as biomarkers for certain diseases or conditions, and can be targeted for therapeutic intervention. For example, drugs that inhibit specific isoenzymes can be used to treat certain types of cancer or heart disease.

Calmodulin is a small, calcium-binding protein that plays a crucial role in regulating various cellular processes in the body. It is found in all eukaryotic cells and is involved in a wide range of physiological functions, including muscle contraction, neurotransmitter release, and gene expression. Calmodulin is a tetramer, meaning that it is composed of four identical subunits, each of which contains two EF-hand calcium-binding domains. When calcium ions bind to these domains, the structure of calmodulin changes, allowing it to interact with and regulate the activity of various target proteins. In the medical field, calmodulin is often studied in the context of various diseases and disorders, including cardiovascular disease, cancer, and neurological disorders. For example, abnormal levels of calmodulin have been associated with the development of certain types of cancer, and calmodulin inhibitors have been investigated as potential therapeutic agents for treating these diseases. Additionally, calmodulin has been implicated in the pathogenesis of various neurological disorders, including Alzheimer's disease and Parkinson's disease.

Cyclic Nucleotide Phosphodiesterases, Type 6 (PDE6) are a family of enzymes that are responsible for breaking down cyclic nucleotides, such as cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), in the retina of the eye. These enzymes play a crucial role in regulating the transmission of visual signals from the retina to the brain. PDE6 is a heterodimeric enzyme composed of two subunits, alpha and beta, which are encoded by different genes. The alpha subunit contains the catalytic site of the enzyme, while the beta subunit is involved in the regulation of the enzyme's activity. Mutations in the genes encoding PDE6 can cause a group of inherited eye disorders known as cone-rod dystrophies, which affect the photoreceptor cells in the retina responsible for color vision and night vision. These disorders are characterized by progressive vision loss and can lead to blindness in affected individuals.

In the medical field, nucleotides are the building blocks of nucleic acids, which are the genetic material of cells. Nucleotides are composed of three components: a nitrogenous base, a pentose sugar, and a phosphate group. There are four nitrogenous bases in DNA: adenine (A), thymine (T), cytosine (C), and guanine (G). There are also four nitrogenous bases in RNA: adenine (A), uracil (U), cytosine (C), and guanine (G). The sequence of these nitrogenous bases determines the genetic information encoded in DNA and RNA.

Dibutyryl cyclic guanosine monophosphate (db-cGMP) is a synthetic analog of cyclic guanosine monophosphate (cGMP), a signaling molecule that plays a crucial role in various physiological processes, including smooth muscle relaxation, neurotransmission, and immune cell function. Db-cGMP is a stable, long-lasting form of cGMP that can be used in research to study the effects of cGMP on cellular signaling pathways. It is often used as a tool to investigate the function of cGMP-dependent protein kinases (PKG) and other signaling proteins that are activated by cGMP. In the medical field, db-cGMP has been studied as a potential therapeutic agent for a variety of conditions, including erectile dysfunction, hypertension, and glaucoma. It has also been used in research to investigate the role of cGMP in various diseases, including cancer, cardiovascular disease, and neurodegenerative disorders.

Theophylline is a medication that is used to treat a variety of respiratory conditions, including asthma, chronic obstructive pulmonary disease (COPD), and bronchitis. It works by relaxing the muscles in the airways, making it easier to breathe. Theophylline is available in both oral and inhaled forms, and it is usually taken on a regular basis to prevent symptoms from occurring. It is important to note that theophylline can have side effects, including nausea, vomiting, and an irregular heartbeat, and it should only be taken under the supervision of a healthcare provider.

Phosphodiesterase I (PDE1) is an enzyme that breaks down cyclic nucleotides, such as cyclic AMP (cAMP) and cyclic GMP (cGMP), into their corresponding monophosphates. These cyclic nucleotides are important signaling molecules in the body that regulate various cellular processes, including muscle contraction, neurotransmission, and gene expression. PDE1 is primarily found in the brain and smooth muscle tissue, where it plays a role in regulating the levels of cAMP and cGMP. In the brain, PDE1 is involved in the regulation of learning, memory, and mood. In smooth muscle tissue, PDE1 is involved in the regulation of blood pressure and heart rate. Inhibition of PDE1 has been shown to have therapeutic potential in the treatment of various conditions, including hypertension, heart failure, and cognitive disorders. However, the use of PDE1 inhibitors can also have side effects, such as headache, nausea, and dizziness.

Cyclic Nucleotide-Gated Cation Channels (CNGCs) are a family of ion channels that are activated by the binding of cyclic nucleotides, such as cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). These channels are found in a variety of cell types, including photoreceptor cells in the retina, olfactory sensory neurons, and neurons in the brain and spinal cord. CNGCs are responsible for mediating a number of physiological processes, including the transduction of light in the retina, the detection of odorants in the nose, and the regulation of neuronal excitability. They are also involved in a number of diseases, including retinitis pigmentosa, olfactory loss, and certain types of epilepsy. CNGCs are composed of five subunits, each of which contains a pore-forming region and a cyclic nucleotide-binding domain. When cyclic nucleotides bind to the cyclic nucleotide-binding domain, it causes a conformational change in the channel that opens the pore and allows cations to flow through. The flow of cations generates an electrical signal that can be detected by the cell.

Phosphorus-Oxygen Lyases are a group of enzymes that catalyze the transfer of a phosphate group from a donor molecule to an acceptor molecule, with the release of oxygen. These enzymes are involved in various metabolic pathways, including the breakdown of certain amino acids and the synthesis of nucleotides. In the medical field, phosphorus-oxygen lyases are of interest because they play a role in the metabolism of certain drugs and toxins, and may be involved in the development of certain diseases. For example, some phosphorus-oxygen lyases are involved in the metabolism of alcohol, and their activity may be altered in individuals with alcohol use disorder. Additionally, some phosphorus-oxygen lyases are involved in the metabolism of certain drugs, and their activity may be affected by the use of these drugs.

Milrinone is a medication that is used to treat heart failure and to improve blood flow in the body. It is a type of medication called a phosphodiesterase inhibitor, which works by relaxing the muscles in blood vessels and increasing the strength of heart contractions. Milrinone is usually given as an intravenous infusion, and it can be used to treat both acute and chronic heart failure. It is also sometimes used to treat low blood pressure during surgery.

Bucladesine is a medication that is used to treat certain types of cancer, including lung cancer and pancreatic cancer. It works by slowing the growth of cancer cells and preventing them from dividing and multiplying. Bucladesine is usually given as an injection into a vein, and it is typically administered in a hospital setting. It is important to note that bucladesine is not a cure for cancer, but it can help to slow the progression of the disease and improve the quality of life for people who are living with cancer.

Pyrrolidinones are a class of organic compounds that contain a five-membered ring with four carbon atoms and one nitrogen atom. They are commonly used in the medical field as intermediates in the synthesis of various drugs and as active ingredients in some medications. One example of a drug that contains a pyrrolidinone moiety is metformin, which is used to treat type 2 diabetes. Metformin is a biguanide, which is a class of drugs that work by reducing the amount of glucose produced by the liver and improving the body's sensitivity to insulin. Pyrrolidinones are also used as chelating agents, which are compounds that bind to metal ions and help to remove them from the body. One example of a pyrrolidinone chelating agent is dimercaprol, which is used to treat heavy metal poisoning, such as from mercury or lead. In addition to their use in medicine, pyrrolidinones have a wide range of other applications, including as solvents, plasticizers, and corrosion inhibitors.

Adenine nucleotides are a type of nucleotide that contains the nitrogenous base adenine (A) and a sugar-phosphate backbone. They are important molecules in the cell and play a crucial role in various biological processes, including energy metabolism and DNA synthesis. There are three types of adenine nucleotides: adenosine monophosphate (AMP), adenosine diphosphate (ADP), and adenosine triphosphate (ATP). AMP is the simplest form of adenine nucleotide, with only one phosphate group attached to the sugar. ADP has two phosphate groups attached to the sugar, while ATP has three phosphate groups. ATP is often referred to as the "energy currency" of the cell because it stores and releases energy through the transfer of phosphate groups. When ATP is broken down, one of its phosphate groups is released, releasing energy that can be used by the cell for various processes. When ATP is synthesized, energy is required to attach a new phosphate group to the molecule. Adenine nucleotides are involved in many cellular processes, including muscle contraction, nerve impulse transmission, and the synthesis of proteins and nucleic acids. They are also important in the regulation of gene expression and the maintenance of cellular homeostasis.

Cyclic AMP-dependent protein kinases (also known as cAMP-dependent protein kinases or PKA) are a family of enzymes that play a crucial role in regulating various cellular processes in the body. These enzymes are activated by the presence of cyclic AMP (cAMP), a second messenger molecule that is produced in response to various stimuli, such as hormones, neurotransmitters, and growth factors. PKA is a heterotetrameric enzyme composed of two regulatory subunits and two catalytic subunits. The regulatory subunits bind to cAMP and prevent the catalytic subunits from phosphorylating their target proteins. When cAMP levels rise, the regulatory subunits are activated and release the catalytic subunits, allowing them to phosphorylate their target proteins. PKA is involved in a wide range of cellular processes, including metabolism, gene expression, cell proliferation, and differentiation. It phosphorylates various proteins, including enzymes, transcription factors, and ion channels, leading to changes in their activity and function. In the medical field, PKA plays a critical role in various diseases and disorders, including cancer, diabetes, and cardiovascular disease. For example, PKA is involved in the regulation of insulin secretion in pancreatic beta cells, and its dysfunction has been implicated in the development of type 2 diabetes. PKA is also involved in the regulation of blood pressure and heart function, and its dysfunction has been linked to the development of hypertension and heart disease.

Cyclic GMP-dependent protein kinases (PKG) are a family of enzymes that play a crucial role in regulating various cellular processes, including smooth muscle contraction, neurotransmitter release, and gene expression. These enzymes are activated by the second messenger molecule cyclic guanosine monophosphate (cGMP), which is produced in response to various stimuli such as nitric oxide (NO) and other signaling molecules. PKG is a serine/threonine kinase that phosphorylates target proteins on specific amino acid residues, leading to changes in their activity or localization. The activity of PKG is tightly regulated by its subcellular localization, substrate availability, and the concentration of cGMP. In the medical field, PKG is of great interest due to its role in various diseases, including cardiovascular disease, hypertension, and erectile dysfunction. PKG inhibitors have been developed as potential therapeutic agents for these conditions, and ongoing research is exploring the potential of PKG activators as novel treatments for various diseases.

Adenylate cyclase is an enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP), a second messenger molecule that plays a crucial role in many cellular signaling pathways. In the medical field, adenylate cyclase is often studied in the context of its role in regulating various physiological processes, including heart rate, blood pressure, and glucose metabolism. It is also involved in the regulation of hormone signaling, particularly in the endocrine system, where hormones such as adrenaline and thyroid hormones bind to specific receptors on the cell surface and activate adenylate cyclase, leading to the production of cAMP and the activation of downstream signaling pathways. Abnormalities in adenylate cyclase activity have been implicated in a number of diseases, including diabetes, hypertension, and certain forms of heart disease. As such, understanding the regulation and function of adenylate cyclase is an important area of research in the medical field.

Papaverine is a medication that is used to treat a variety of medical conditions, including erectile dysfunction, Raynaud's disease, and glaucoma. It is a vasodilator, which means that it helps to widen blood vessels and improve blood flow. Papaverine is usually administered intravenously or intramuscularly, and it can cause side effects such as headache, nausea, and dizziness. It is important to note that papaverine should only be used under the supervision of a healthcare professional.

I'm sorry, but I'm not aware of any medical term or abbreviation called "Cyclic IMP." It's possible that you may have misspelled the term or that it is a term used in a specific medical field or specialty that I am not familiar with. If you could provide more context or information about where you heard or saw this term, I may be able to provide a more accurate answer.

Colforsin is a synthetic decapeptide that mimics the action of adenosine, a naturally occurring molecule that plays a role in regulating various physiological processes in the body. It is used in the medical field as a bronchodilator, which means it helps to relax and widen the airways in the lungs, making it easier to breathe. Colforsin is typically administered as an aerosol or nebulizer solution and is used to treat conditions such as asthma, chronic obstructive pulmonary disease (COPD), and bronchitis. It works by activating adenosine receptors in the lungs, which leads to the release of calcium from the cells lining the airways, causing them to relax and open up.

Guanylate cyclase is an enzyme that plays a crucial role in the regulation of various physiological processes in the body, including blood pressure, smooth muscle contraction, and immune function. It is a membrane-bound protein that catalyzes the conversion of guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP), a second messenger molecule that regulates the activity of various proteins in the cell. In the cardiovascular system, guanylate cyclase is activated by nitric oxide (NO), a signaling molecule that is released by endothelial cells in response to various stimuli, such as shear stress or the presence of certain hormones. Activation of guanylate cyclase by NO leads to an increase in cGMP levels, which in turn causes relaxation of smooth muscle cells in blood vessels, leading to vasodilation and a decrease in blood pressure. Guanylate cyclase is also involved in the regulation of immune function, as it is activated by various immune cells and cytokines. Activation of guanylate cyclase by immune cells leads to the production of cGMP, which regulates the activity of immune cells and helps to maintain immune homeostasis. In addition, guanylate cyclase is involved in the regulation of various other physiological processes, such as neurotransmission, vision, and hearing. It is a key enzyme in the regulation of these processes and plays a crucial role in maintaining normal physiological function.

8-Bromo Cyclic Adenosine Monophosphate (8-Br-cAMP) is a synthetic analog of cyclic adenosine monophosphate (cAMP), a signaling molecule that plays a crucial role in various cellular processes, including cell growth, differentiation, and metabolism. In the medical field, 8-Br-cAMP is used as a tool to study the effects of cAMP on cellular signaling pathways. It is often used in cell culture experiments to increase intracellular cAMP levels and investigate the downstream effects on gene expression, protein synthesis, and cellular behavior. 8-Br-cAMP is also used in some clinical applications, such as the treatment of certain types of cancer. It has been shown to inhibit the growth of some cancer cells by blocking the activity of certain enzymes involved in cell proliferation. However, more research is needed to fully understand the potential therapeutic applications of 8-Br-cAMP in medicine.

Calcium is a chemical element with the symbol Ca and atomic number 20. It is a vital mineral for the human body and is essential for many bodily functions, including bone health, muscle function, nerve transmission, and blood clotting. In the medical field, calcium is often used to diagnose and treat conditions related to calcium deficiency or excess. For example, low levels of calcium in the blood (hypocalcemia) can cause muscle cramps, numbness, and tingling, while high levels (hypercalcemia) can lead to kidney stones, bone loss, and other complications. Calcium supplements are often prescribed to people who are at risk of developing calcium deficiency, such as older adults, vegetarians, and people with certain medical conditions. However, it is important to note that excessive calcium intake can also be harmful, and it is important to follow recommended dosages and consult with a healthcare provider before taking any supplements.

Guanine nucleotides are a type of nucleotide that contains the nitrogenous base guanine. They are important components of DNA and RNA, which are the genetic material of all living organisms. In DNA, guanine nucleotides are paired with cytosine nucleotides to form the base pair G-C, which is one of the four possible base pairs in DNA. In RNA, guanine nucleotides are paired with uracil nucleotides to form the base pair G-U. Guanine nucleotides play a crucial role in the structure and function of DNA and RNA, and are involved in many important biological processes, including gene expression, DNA replication, and protein synthesis.

Isoproterenol is a synthetic beta-adrenergic agonist that is used in the medical field as a medication. It is a drug that mimics the effects of adrenaline (epinephrine) and can be used to treat a variety of conditions, including asthma, heart failure, and bradycardia (a slow heart rate). Isoproterenol works by binding to beta-adrenergic receptors on the surface of cells, which triggers a cascade of events that can lead to increased heart rate, relaxation of smooth muscle, and dilation of blood vessels. This can help to improve blood flow and oxygen delivery to the body's tissues, and can also help to reduce inflammation and bronchoconstriction (narrowing of the airways). Isoproterenol is available in a variety of forms, including tablets, inhalers, and intravenous solutions. It is typically administered as a short-acting medication, although longer-acting formulations are also available. Side effects of isoproterenol can include tremors, palpitations, and increased heart rate, and the drug may interact with other medications that affect the heart or blood vessels.

Xanthines are a group of compounds that include caffeine, theophylline, and theobromine. They are naturally occurring alkaloids found in plants such as coffee, tea, and cocoa. In the medical field, xanthines are used as bronchodilators to treat conditions such as asthma and chronic obstructive pulmonary disease (COPD). They work by relaxing the muscles in the airways, allowing air to flow more easily. Xanthines can also be used to treat heart rhythm disorders and to prevent blood clots. However, they can have side effects such as nausea, vomiting, and increased heart rate, and may interact with other medications.

Vinca alkaloids are a group of naturally occurring compounds derived from the Madagascar periwinkle plant (Vinca rosea). They are used in the treatment of various types of cancer, including leukemia, lymphoma, and solid tumors such as breast, ovarian, and lung cancer. Vinca alkaloids work by binding to microtubules, which are essential components of the cell's cytoskeleton. By binding to microtubules, vinca alkaloids prevent the formation of new microtubules and stabilize existing ones, leading to cell death. The most commonly used vinca alkaloids in cancer treatment are vinblastine and vincristine. These drugs are typically administered intravenously and can cause a range of side effects, including nausea, vomiting, hair loss, and peripheral neuropathy (numbness or tingling in the hands and feet). However, they are often effective in controlling the growth of cancer cells and can be used in combination with other chemotherapy drugs to improve treatment outcomes.

In the medical field, cyclic P-oxides refer to a class of organic compounds that contain a ring of atoms with a double bond between two oxygen atoms and a single bond between one of the oxygen atoms and a phosphorus atom. These compounds are also known as phosphorus oxides or phosphorus ylides. Cyclic P-oxides are often used as intermediates in organic synthesis reactions, particularly in the synthesis of heterocyclic compounds such as pyrroles, furans, and thiophenes. They can also be used as reagents in organic reactions, such as in the Staudinger reduction, which is a method for converting aldehydes and ketones into primary amines. In addition to their use in organic synthesis, cyclic P-oxides have also been studied for their potential medicinal applications. For example, some cyclic P-oxides have been shown to have antitumor activity, and they are being investigated as potential treatments for cancer. Other cyclic P-oxides have been studied for their potential to treat neurological disorders, such as Alzheimer's disease and Parkinson's disease.

"Cryo-EM structure of phosphodiesterase 6 reveals insights into the allosteric regulation of type I phosphodiesterases". Science ... cyclic 3',5'-nucleotide phosphodiesterase, cyclic 3′,5′-phosphodiesterase, 3′,5′-nucleotide phosphodiesterase, 3':5'-cyclic ... monophosphate phosphodiesterase (cyclic CMP), cyclic 3′,5-nucleotide monophosphate phosphodiesterase, nucleoside 3′,5′-cyclic ... cyclic AMP 3′,5′-cyclic dAMP 3′,5′-cyclic IMP 3′,5′-cyclic GMP 3′,5′-cyclic CMP There are 11 distinct phosphodiesterase ...
"Isozyme selective inhibition of cGMP-stimulated cyclic nucleotide phosphodiesterases by erythro-9-(2-hydroxy-3-nonyl) adenine ... which also acts as a phosphodiesterase inhibitor that selectively inhibits phosphodiesterase type 2 (PDE2). "Sigma Aldrich". ... adenine inhibits cyclic GMP-stimulated phosphodiesterase in isolated cardiac myocytes". Molecular Pharmacology. 48 (1): 121-30 ... EHNA (erythro-9-(2-hydroxy-3-nonly)adenine) is a potent adenosine deaminase inhibitor, ...
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 ...
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 ...
... 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 ... 45 (2): 388-402. doi:10.1007/s12035-012-8250-4. hdl:10261/60667. PMID 22396213. S2CID 12709387. Weiss JL, Hui H, Burgoyne RD ( ...
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. " ... High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B is an enzyme that in humans is encoded by ...
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 ...
Cyclic-nucleotide 3'-phosphodiesterase, a myelin-associated enzyme that makes up 4% of total CNS myelin protein Chronic ... nonbacterial prostatitis, a pelvic pain condition affecting men c-type Natriuretic Peptide, a vasoactive hormone Certified ... a proposed class of living organisms smaller than the accepted lower limit size for life 2',3'- ...
"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 ...
"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 ...
Modulates the activity of membrane-bound enzymes: phosphodiesterase, cyclic nucleotides, adenylate cyclase, aldoreductase, ... Its chemical structure resembles that of pyridoxine (a type of vitamin B6). Emoxypine was first synthesized by L.D. Smirnov and ... Emoxypine (2-ethyl-6-methyl-3-hydroxypyridine), also known as Mexidol or Mexifin when used as the succinate salt, is an ... Gruber W (1953). "Synthesis of 3-Hydroxy-2-alkylpyridines". Canadian Journal of Chemistry. 31 (6): 564-568. doi:10.1139/v53-079 ...
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 ( ... Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1C is an enzyme that in humans is encoded by the PDE1C ... Rybalkin SD, Rybalkina I, Beavo JA, Bornfeldt KE (2002). "Cyclic nucleotide phosphodiesterase 1C promotes human arterial smooth ...
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. ...
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 ...
"Positive inotropic effect of the inhibition of cyclic GMP-stimulated 3',5'-cyclic nucleotide phosphodiesterase (PDE2) on guinea ... As different PDE types may affect different cAMP pools, the different PDEs may regulate different processes in the cell. PDE2 ... "Biologic regulation through opposing influences of cyclic GMP and cyclic AMP: the Yin Yang hypothesis". Adv Cyclic Nucleotide ... June 1997). "cGMP-stimulated cyclic nucleotide phosphodiesterase regulates the basal calcium current in human atrial myocytes ...
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 ...
... is a cyclic nucleotide derivative which mimics the action of endogenous cAMP and is a phosphodiesterase inhibitor. ... The effect of bucladesine as a cAMP analog has been studied on the pentylenetetrazol-induced seizure in the wild-type mice. The ... Bucladesine (50-100nM/mouse) showed significant attenuation in the morphine withdrawal syndrome in the wild-type mice. In ... Nucleotides, Carboxamides, PDE3 inhibitors, All stub articles, Cardiovascular system drug stubs). ...
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 ...
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 ...
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 ...
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 ...
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-GMP phosphodiesterase MeSH D08.811.277.352.640.150 - 3',5'-cyclic-nucleotide phosphodiesterase MeSH D08.811.277.352. ... myosin type iii MeSH D08.811.277.040.025.525.843 - myosin type iv MeSH D08.811.277.040.025.525.875 - myosin type v MeSH D08.811 ... cyclic-nucleotide phosphodiesterases MeSH D08.811.277.352.640.295 - glycerophosphoinositol inositolphosphodiesterase MeSH ... cyclic nucleotide-regulated protein kinases MeSH D08.811.913.696.620.682.700.150.125 - cyclic amp-dependent protein kinases ...
"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 ... Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit beta is the beta subunit of the protein complex PDE6 that is encoded ...
Lugnier, C. (2006). "Cyclic nucleotide phosphodiesterase (PDE) superfamily: A new target for the development of specific ... "Phosphodiesterase type-5 inhibitor use in type 2 diabetes is associated with a reduction in all-cause mortality". Heart. 102 ( ... Yu, J. Y.; Kang, K. K. & Yoo, M. (2006). "Erectile potentials of a new phosphodiesterase type 5 inhibitor, DA-8159, in diet- ... McMahon, C. G.; McMahon, C. N.; Leow, L. J. & Winestock, C. G. (2006). "Efficacy of type-5 phosphodiesterase inhibitors in the ...
... 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) ... Rodent studies have consistently shown upregulation of the 3, 5-cyclic adenosine monophosphate (cAMP) system induced by ... "Interaction between the antidepressant-like behavioral effects of beta adrenergic agonists and the cyclic AMP PDE inhibitor ...
"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 ...
... phosphodiesterase EC 3.1.4.17: 3′,5′-cyclic-nucleotide phosphodiesterase EC 3.1.4.18: Now EC 3.1.16.1, spleen exonuclease EC ... 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, ... cyclic-guanylate-specific phosphodiesterase EC 3.1.4.53: 3′,5′-cyclic-AMP phosphodiesterase EC 3.1.4.54: N- ...
Weiss B, Hait WN (1977). "Selective cyclic nucleotide phosphodiesterase inhibitors as potential therapeutic agents". Annual ... is a vasodilating drug that works by blocking the degradative action of cGMP-specific phosphodiesterase type 5 (PDE5) on cyclic ... 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-nucleotide 3'-phosphodiesterase and multiple molecules of the immune system. GRCh38: Ensembl release 89: ENSG00000197971 ... In general, the major form of MBP is a protein of about 18.5 Kd (170 residues). In melanocytic cell types, MBP gene expression ... 53 (2): 189-197. doi:10.1002/ana.10425. PMID 12557285. S2CID 43317994. Namer IJ, Steibel J, Poulet P, Armspach JP, Mohr M, ... 349 (2): 139-145. doi:10.1056/NEJMoa022328. PMID 12853586. Pfister HW, Einhäupl KM, Wick M, Fateh-Moghadam A, Huber M, Schielke ...
... arginase and phosphodiesterase-5) and type-2 diabetes (α-amylase and α-glucosidase) were determined. Antioxidant properties of ... phosphodiesterase-5 (IC 50 =539.72 µg/mL); arginase (41.53 µg/mL)] than CG [phosphodiesterase-5 (IC 50 =611.35 µg/mL); arginase ... Conclusions The ability of samples extract to inhibit some of key enzymes relevant to erectile dysfunction and type-2 diabetes ... Also, both extracts inhibited phosphodiesterase-5 and arginase in a dose-dependent manner in vitro ; nevertheless, HU showed ...
Cyclic Nucleotide Phosphodiesterases, Type 2. *Gene Knockdown Techniques. _. Top Journals Top journals in which articles about ...
... cyclic nucleotide 3-phosphodiesterase), along with the M. leprae antigen PGL-1 in the peripheral nerve biopsy specimens. In ... We found that the expression of the C-type lectin, CD209, known to be expressed on tissue macrophages and to mediate the uptake ... By integrating the spatial coordinates of the key cell types and antimicrobial gene expression in RR and T-lep lesions, we ... The ability of microbial pathogens to target specific cell types is a key aspect of the pathogenesis of infectious disease. ...
Cyclic nucleotide-3′-phosphodiesterase. There are many higher molecular weight proteins present in the gel-electrophoretic ... Alginate from two Chilean seaweed types particularly suitable. Two seaweed species that grow on the coast of Chile form the ... cyclic nucleotide-3′-phosphodiesterase (CNP), which comprises several percent of myelin protein [23]. Although there are low ... This is probably an artifactual activity; recall that the biologically active cyclic nucleotides are those with a 3′:5′ ...
May stimulate a membrane Ca2+-ATPase and a 3,5-cyclic nucleotide phosphodiesterase. Ref: uniprot.org ... Alternative Names Calbindin D28,D-28K, Vitamin D-dependent calcium-binding protein, avian-type ... Alternative Names Calbindin D28,D-28K, Vitamin D-dependent calcium-binding protein, avian-type ... and selectively expressed in certain type of interneurons (calbindin-postive interneuron) in the cortex (middle). Methyl-CpG ...
Cyclic nucleotide phosphodiesterases in health and disease. It has recently in europe. Laparoscopic adrenalectomy laparoscopic ... selfhood that the the significance of type of person who was given by cardiologists in secondary gonadotropin deficiency (see ... Heterozygous reductase-2 deficiency. Diminished capacity to dysfunctional sexual re- wards or a penile prosthesis (ipp), which ...
The ability of methylxanthines to inhibit cyclic nucleotide phosphodiesterases is often cited to explain their therapeutic ... Adverse experiences were similar in type and severity to those previously associated with a single dose of acetaminophen, ... Thus, phosphodiesterase inhibition is probably not important to the therapeutic effects of methylxanthines. ... Plasma caffeine concentrations that raise blood pressure are below the threshold for phosphodiesterase inhibition. ...
Type 5 Cyclic Nucleotide Phosphodiesterases 18% 18 Scopus citations * Comparing routine versus selective use of intraoperative ... Moran, C. J., Mar 1 2020, In: American Journal of Neuroradiology. 41, 3, p. 486-487 2 p.. Research output: Contribution to ... 2 othersCekirge, S. H. & Nelson, P. K., Jul 2017, In: Journal of neurosurgery. 127, 1, p. 81-88 8 p.. Research output: ... 2 othersMarosfoi, M. & Nelson, P. K., Jan 1 2017, In: Neurosurgery. 80, 1, p. 40-48 9 p.. Research output: Contribution to ...
Evolutionary conservation of cyclic nucleotide phosphodiesterases. Campus Life Did You know? Institute vesting order was signed ... Such translation is of two types. One, to startups from the institution itself. Two, technology transfer to established ... Version 2 will automate the financial part and is set for release in 2021. Version 3 will bring in artificial intelligence ...
Mouse anti-23 cyclic nucleotide phosphodiesterase (CNPase) was bought from Sigma. Rabbit polyclonal -adducin antibodies have ... To check this hypothesis, we ready crude mind membranes from adult caspr-null (caspr KO) and wild-type (WT) littermate mice. ... as well as the Daminozide glial 155 kD type of neurofascin (NF-155). Earlier studies have proven these three proteins are ... Diana M. Gilligan (College or university of Washington College of Medication). Rabbit polyclonal anti-septin 2 antibodies were ...
Given its ability to transport important intra- and intercellular mediators such as cyclic nucleotides and eicosanoids, the ... For the same reason, it is also implicated in the progression of multiple cancer types [10] including acute myeloid leukemia [ ... phosphodiesterase inhibitors: sildenafil, zaprinast, trequinsin;. cardiovascular drugs: verapamil, losartan, telmisartan, ... MRP4 overexpression confers cellular resistance to nucleotide-base, nucleoside, and nucleotide analogues, as well as to certain ...
... 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 ...
PDEs degrade cyclic nucleotides towards the particular nucleotide monophosphates by hydrolysis from the phosphodiester ... However there is significant heterogeneity within and between tumor types. It was noted that different tumor types have ... and phosphodiesterase (PDE), which catalyze the degradation or synthesis of cAMP, respectively. Several research workers have ... using the focus of cyclic nucleotide time for basal amounts in around 1 min. To create this speedy transformation in cAMP ...
Invitrogen Anti-Phospho-Calmodulin 1/2/3 (Thr79, Ser81) Polyclonal, Catalog # PA5-104932. Tested in Western Blot (WB), ... positive regulation of cyclic-nucleotide phosphodiesterase activity response to corticosterone response to calcium ion ... cookie.CK_DISPLAY_TYPE.value:. pageContext.request.scheme:http(not used). syndicationProtocol:https. syndicationExtensionPrefix ... positive regulation of cyclic nucleotide metabolic process positive regulation of protein autophosphorylation regulation of ...
Cyclic-GMP Phosphodiesterase. 3,5-Cyclic-GMP Phosphodiesterases. 3,5-Cyclic-Nucleotide Phosphodiesterase. 3,5-Cyclic-AMP ... 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 ...
Cyclic-GMP Phosphodiesterase. 3,5-Cyclic-GMP Phosphodiesterases. 3,5-Cyclic-Nucleotide Phosphodiesterase. 3,5-Cyclic-AMP ... 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 ...
Cyclic-GMP Phosphodiesterase. 3,5-Cyclic-GMP Phosphodiesterases. 3,5-Cyclic-Nucleotide Phosphodiesterase. 3,5-Cyclic-AMP ... 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 ...
Cyclic-GMP Phosphodiesterase. 3,5-Cyclic-GMP Phosphodiesterases. 3,5-Cyclic-Nucleotide Phosphodiesterase. 3,5-Cyclic-AMP ... 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 ...
Cyclic-GMP Phosphodiesterase. 3,5-Cyclic-GMP Phosphodiesterases. 3,5-Cyclic-Nucleotide Phosphodiesterase. 3,5-Cyclic-AMP ... 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 ...
Cyclic-GMP Phosphodiesterase. 3,5-Cyclic-GMP Phosphodiesterases. 3,5-Cyclic-Nucleotide Phosphodiesterase. 3,5-Cyclic-AMP ... 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 ...
Cyclic-GMP Phosphodiesterase. 3,5-Cyclic-GMP Phosphodiesterases. 3,5-Cyclic-Nucleotide Phosphodiesterase. 3,5-Cyclic-AMP ... 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 ...
Cyclic-GMP Phosphodiesterase. 3,5-Cyclic-GMP Phosphodiesterases. 3,5-Cyclic-Nucleotide Phosphodiesterase. 3,5-Cyclic-AMP ... 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 ...
Cyclic-GMP Phosphodiesterase. 3,5-Cyclic-GMP Phosphodiesterases. 3,5-Cyclic-Nucleotide Phosphodiesterase. 3,5-Cyclic-AMP ... 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 ...
Type III cGMP-inhibited cyclic nucleotide phosphodiesterases (PDE3 gene family). Cell Signal. 7, 445-455, 1995.. Marques LJ, ... Cyclic nucleotide phosphodiesterases. J Allergy Clin Immunol. 108, 671-680, 2001.. Fertel R, Weiss B. Properties and drug ... Cyclic nucleotide phosphodiesterases: relating structure and function. Prog Nucleic Acid Res Mol Biol. 65, 1-52, 2001.. ... Mehats C, Andersen CB, Filopanti M, Jin SL, Conti M. Cyclic nucleotide phosphodiesterases and their role in endocrine cell ...
Signs and symptoms of TBRF include cyclic febrile episodes, nausea, and vomiting (1). The bacterium Borrelia turicatae is the ... Plasmid Analysis and Genetic Typing of Relapsing Fever Spirochete Isolates. We performed reverse-field electrophoresis to ... nucleotide identity to the 91E135 and BTE5EL isolates of B. turicatae. Isolates 91E135 and BTE5EL originated from field- ... turicatae glycerophosphodiester phosphodiesterase (glpQ) gene (forward primer 5′-GCCTGTCAGAATGAAAAA-3′, reverse primer 5′- ...
Cyclic-Nucleotide Phosphodiesterases [D08.811.277.352.640.160] * Glycerophosphoinositol Inositolphosphodiesterase [D08.811. ... Phosphodiesterase I [D08.811.277.352.640.430] * Phospholipases [D08.811.277.352.640.700] * Type C Phospholipases [D08.811. ... 3,5-Cyclic-AMP Phosphodiesterases [D08.811.277.352.640.150] * 3,5-Cyclic-GMP Phosphodiesterases [D08.811.277.352.640.155] ...
AIMS: Levels of the cyclic nucleotides guanosine 3, 5-monophosphate (cGMP) or adenosine 3, 5-monophosphate (cAMP) that play ... In contrast, CS did not induce any of these molecular changes in wild-type mice. The present findings suggest beneficial and ... phosphodiesterases (PDEs)] in the brain of AD patients vs. METHODS: For cGMP and cAMP CSF analysis, the cohort (n¿=¿79) ... VGLUT1+/- mice (C57BL/6) and wild type (WT) littermates were used. VGLUT1 expression in the DRN, 5-HT turnover and immuno ...
3. cGMP-specific phosphodiesterase. 4. cAMP-specific phosphodiesterase. 92. Cellular level of tumour suppressor protein p53 is ... C. ABA-responsive genes contain six- nucleotide ABRE elements in the promoter.. D. Nine-nucleotide dehydration-responsive ... 1. Cyclic GMP. 2. Diacylglycerol. 3. Inositol triphosphate. 4. Phosphatidyl inositol. 37. In chick, development of wing feather ... 4. Both types of cells show permissive instruction. 96. Following are certain statements regarding morphogen gradients and cell ...
photoreceptor cyclic-nucleotide phosphodiesterase activity GO:0004120 * arginine N-succinyltransferase activity GO:0008791 ... Type: http://bio2vec.net/ontology/gene_function Label: inositol phosphosphingolipid phospholipase activity ...
  • The histopathological diagnoses in total group were as follows: (borderline tuberculoid (BT) = 52, tuberculoid (TT) = 8, borderline lepromatous (BL) = 8, borderline borderline (BB) = 3, nonspecific inflammation = 3, healed/fibrosed = 4, and axonopathy = 2). (bvsalud.org)
  • Since caffeine is a non-specific phosphodiesterase inhibitor, we investigated the effects of several PDE inhibitors on the formation of sunburn cells in mouse skin after an acute exposure to ultraviolet light B (UVB). (nih.gov)
  • 6. Enhancement of motility and acrosome reaction in human spermatozoa: differential activation by type-specific phosphodiesterase inhibitors. (nih.gov)
  • Exposure of hybrid cells for 3-7 days to PGE1, which results in activation of adenylate cyclase, or exposure to various cyclic nucleotide phosphodiesterase inhibitors, markedly increases the number of synapses formed. (nih.gov)
  • Since PDE2 hydrolyzes cyclic nucleotides, mainly cGMP, the effects of EHNA hydrochloride on epidermal apoptosis following UVB exposure may be mediated, in part, by increased cGMP signaling. (nih.gov)
  • The vasodilatory and antiplatelet actions of cilostazol are due mainly to the inhibition of phosphodiesterase 3 (PDE3) and subsequent elevation of intracellular cAMP levels. (nih.gov)
  • 5. Development of human and rabbit vaginal smooth muscle cell cultures: effects of vasoactive agents on intracellular levels of cyclic nucleotides. (nih.gov)
  • 16. Bovine sperm capacitation: assessment of phosphodiesterase activity and intracellular alkalinization on capacitation-associated protein tyrosine phosphorylation. (nih.gov)
  • Receptor-mediated increases in intracellular cyclic AMP or cyclic GMP levels had no immediate effect on K+-dependent 45Ca2+ uptake by cells or on acetylcholine secretion from cells. (nih.gov)
  • Aunque las enzimas de tipo 2 se clasifican como fosfodiesterasas 3',5' AMP cíclico (EC 3.1.4.17), los miembros de esta clase tienen una especificidad adicional para el GMP CÍCLICO. (bvsalud.org)
  • 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 . (bvsalud.org)
  • A cyclic nucleotide phosphodiesterase subfamily that is activated by the binding of CYCLIC GMP to an allosteric domain found on the enzyme. (bvsalud.org)
  • 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. (bvsalud.org)
  • These results show that cell lines with or without defects in synapse formation can be generated and that voltage-sensitive Ca2+ channel activity can be regulated by a receptor-mediated reaction which is coupled to activation of adenylate cyclase, or by inhibition of adenlyate clyclase, or by inhibition of cyclic nucleotide phosphodies-terase. (nih.gov)
  • 15. Interaction between Ca2+, cyclic 3',5' adenosine monophosphate, the superoxide anion, and tyrosine phosphorylation pathways in the regulation of human sperm capacitation. (nih.gov)
  • 18. Cyclic AMP efflux, via MRPs and A1 adenosine receptors, is critical for bovine sperm capacitation. (nih.gov)
  • 9. Type 5 phosphodiesterase regulation of human sperm motility. (nih.gov)
  • 4. Sildenafil inhibits phosphodiesterase type 5 in human clitoral corpus cavernosum smooth muscle. (nih.gov)
  • D600 inhibits 45Ca2+ uptake dependent on 80 mM K+ (IC50 = 2 X 10^(-7) M), but has little or no effect on 45Ca2+ uptake in the presence of 5 mM K+. (nih.gov)
  • 19. Effect of sildenafil on cyclic nucleotide phosphodiesterase activity, vascular tone and calcium signaling in rat pulmonary artery. (nih.gov)
  • The effects of putative neurotransmitters or hormones on intra-cellular cyclic AMP or cyclic GMP levels, voltage-sensitive Ca2+ channel activity, and acetylcholine secretion were determined. (nih.gov)
  • Over fifty members of this family exist, most of which bind specifically to regulatory subunits of CYCLIC-AMP-DEPENDENT PROTEIN KINASE TYPE II such as CAMP PROTEIN KINASE RIIALPHA or CAMP PROTEIN KINASE RIIBETA. (nih.gov)
  • 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)
  • 2] However, caffeine was considered in one study as a potential drug of abuse and has even been described as a model drug of abuse. (medscape.com)
  • This study is a family-based genetic association analysis examining the myelin-associated glycoprotein (MAG) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) genes in schizophrenia. (nih.gov)
  • ADPKD-omics": determinants of cyclic AMP levels in renal epithelial cells. (nih.gov)
  • A functional evaluation based on the effects of the single nucleotide variant (SNV) associated with PB leprosy on the specific immune response was also performed. (bvsalud.org)
  • However, prolonged exposure of hybrid cells to PGE1 results both in an increase in cellular cyclic AMP and the gradual acquisition by cells of functional voltage-sensitive Ca2+ channels. (nih.gov)
  • The growing epidemic of obesity-associated type 2 diabetes represents one of the major threats to human health in the 21st century. (nih.gov)
  • To gain insight into the pathophysiology of type 2 diabetes and to develop new treatment protocols, it is essential to characterize the molecular components and signaling networks critical for beta-cell function and glucose and energy homeostasis. (nih.gov)
  • During the past few years, NIH researchers have used gene targeting and transgenic techniques to develop novel mouse models to study the molecular basis of type 2 diabetes and glucose and energy homeostasis. (nih.gov)
  • Its overexpression in agouti mice results in uniform yellow coat color, OBESITY, and metabolic defects similar to type II diabetes in humans. (nih.gov)
  • 1. The cyclic GMP-specific phosphodiesterase inhibitor, sildenafil, stimulates human sperm motility and capacitation but not acrosome reaction. (nih.gov)
  • 17. Cyclic nucleotide phosphodiesterases in human spermatozoa and seminal fluid: Presence of an active PDE10A in human spermatozoa. (nih.gov)
  • About 246 families of primarily European-Caucasian origin were genotyped for MAG rs2301600, rs720308, rs720309, rs756796, and CNP rs2070106 single nucleotide polymorphisms (SNPs). (nih.gov)
  • We transected the dorsal two-thirds of the spinal cords of wild-type mice at vertebral level Th8/9, leaving only the fibers in the ventral funiculus intact. (medscape.com)
  • The FBAT program (v1.7.2) and Transmit were used to analyze individual SNPs and haplotypes, respectively. (nih.gov)
  • f) TUNEL staining of apoptotic cells in wild-type animals subjected to SCI and treated i.p. with antibodies to CD95L and/or TNF. (medscape.com)
  • Case-control association study of the 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) gene and schizophrenia in the Han Chinese population. (nih.gov)
  • 11. Mammalian sperm phosphodiesterases and their involvement in receptor-mediated cell signaling important for capacitation. (nih.gov)
  • The 2 major coffee types are arabica (Coffea arabica) and robusta (Coffea canephora). (medscape.com)