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Phosphodiesterase human

Currently, one of the most well-known, promising therapeutic drugs in relation to endogenous NO is sildenafil. The main phosphodiesterase in the human... [Pg.859]

Trequinsin 106, a selective phosphodiesterase-3 (PDE3) inhibitor <2005MI6412>, and actisomide 225 have been introduced into human therapy as antihypertensive and antiarrhythmic agents, respectively. [Pg.115]

Fisher DA et al. Isolation and characterization of PDE9A, a novel human cGMP-specific phosphodiesterase. J Biol Chem 1998 273 15559-15564. [Pg.124]

Fawcett, L., Baxendale, R., Stacey, P. et al. Molecular cloning and characterrization of a distinct human phosphodiesterase gene familly PDE11A. Proc. Natl Acad. Sci. U.S.A. 97 3702-3707, 2000. [Pg.377]

Mehorta and coworkers (1989) observed that isolated fractions of brain and heart cells from rats orally administered 0.5-10 mg endrin/kg showed significant inhibition of Ca+2 pump activity and decreased levels of calmodulin, indicating disruption of membrane Ca+2 transport mechanisms exogenous addition of calmodulin restored Ca+2-ATPase activity. In vitro exposure of rat brain synaptosomes and heart sarcoplasmic reticuli decreased total and calmodulin-stimulated calcium ATPase activity with greater inhibition in brain preparations (Mehorta et al. 1989). However, endrin showed no inhibitory effects on the calmodulin-sensitive calcium ATPase activity when incubated with human erythrocyte membranes (Janik and Wolf 1992). In vitro exposure of rat brain synaptosomes to endrin had no effect on the activities of adenylate cyclase or 3, 5 -cyclic phosphodiesterase, two enzymes associated with synaptic cyclic AMP metabolism (Kodavanti et al. 1988). [Pg.74]

T. R., LalibertO, F., Lynch, J.J., Mancini, J., Martins, E., Masson, P., Muise, E., Pon, D. J., Siegl, P.KS., Styhler, A., Tsou, N.N., Turner, M.J., Young, R.N. and Girard, Y. (2003) Optimization of a tertiary alcohol series of phosphodiesterase-4 (PDE4) inhibitors structure-activity relationship related to PDE4 inhibition and human ether-a-go-go related gene potassium... [Pg.454]

Phosphatases are numerous and important enzymes (see also Chapt. 2). They are classified as phosphoric monoester hydrolases (phosphatases, EC 3.1.3), phosphoric diester hydrolases (phosphodiesterases, EC 3.1.4), triphosphoric monoester hydrolases (EC 3.1.5), diphosphoric monoester hydrolases (pyrophosphatases, EC 3.1.7), and phosphoric triester hydrolases (EC 3.1.8) [21] [63]. Most of these enzymes have a narrow substrate specificity restricted to endogenous compounds. However, some of these enzymes are active toward xenobiotic organophosphorus compounds, e.g., alkaline phosphatase (EC 3.1.3.1), acid phosphatase (EC 3.1.3.2), aryldialkylphosphatase (para-oxonase (PON1), EC 3.1.8.1) and diisopropyl-fluorophosphatase (tabunase, somanase, EC 3.1.8.2) [64 - 70]. However, such a classification is far from definitive and will evolve with further biochemical findings. Thus, a good correlation has been found in human blood samples between somanase and sarinase activities on the one hand, and paraoxonase (PON1) type Q isozyme concentrations on the other [71]. [Pg.567]

Dichlorvos (9.50) is an insecticide of reportedly wide use, the metabolites of which in humans include dichloroethanol and dimethyl phosphate. Like paraoxon, dichlorvos is hydrolyzed by human serum. However, the enzyme activities hydrolyzing the two substrates were shown to differ by a number of criteria [114], Clearly large gaps remain in our understanding of the human metabolism of organophosphorus insecticides and other toxins. A bacterial phosphodiesterase appears as a promising tool to understand the catalytic mechanisms of organophosphoric acid triester detoxification [115-117],... [Pg.580]

Phosphodiesterases PDE2 Human cell line Inflammation, congestive heart failure, arrythmias, obesity Cardiac positive inotropy and chronotropy... [Pg.124]

Tetrahydropyrazolo[3,4-f]pyridines have been prepared as cannabinoid modulators <2007W0112399>. The pyra-zolo[3,4-4pyridine, Apixaban (BMS-562247), has been found to be a highly potent, selective, efficacious, and orally bioavailable inhibitor of blood coagulation factor xa <2007JMC5339>. Several pyrazolo[3,4-f]pyridines have been found to be potent inhibitors of human eosinophil phosphodiesterase <2007JMC344>. [Pg.487]

Administration of a cocktail containing eicosapentenoic acid and docosahexenoic acid to volunteers for up to 6 weeks, resulted in a significant depression in IL-1J3 (61%), IL-1 a (39%), and TNF (40%) synthesis. These levels returned to normal after a few weeks [99]. In vitro studies indicate that Pentoxifylline can block the effects of IL-1 and TNF on neutrophils [100]. It is a phosphodiesterase (PDE) inhibitor that causes increased capillary blood flow by decreasing blood viscocity and is used clinically in chronic occlusive arterial disease of the limbs with intermittent claudication. Denbufylline, a closely related xanthine, has been patented as a functional inhibitor of cytokines and exhibits a similar profile to Pentoxifylline [101]. Romazarit (Ro-31-3948) derived from oxazole and isoxazole propionic acids has been shown to block IL- 1-induced activation of human fibroblasts in vitro and in animal models reduces inflammation [102,103,104]. By using a spontaneous autoimmune MRL/lpr mouse model, a significant efficacy was shown [105]. Two-dimensional structures of some of these molecules are shown in Figure 14. [Pg.427]

Lam, S.C.T. Packham, M.A. Isolation and kinetic studies of nucleoside diphosphokinase from human platelets and effects of cAMP phosphodiesterase inhibitors. Biochem. Pharmacol., 35, 4449-4455 (1986)... [Pg.534]

In another approach subcellular fractionation of human PMNs, stimulated in vitro with phorbol myristate acetate or opsonized zymsan, was performed by rate-zonal centrifugation in sucrose gradients By varying the centrifugal force the NADPH oxidase could be separated from the activities of enzymes in the lysosomal granules but was similar to the distribution of markers for the plasma membrane, aryl phosphatase, alkaline phosphodiesterase I, and acid aryl phosphatase. [Pg.48]

A quantitative indication of the importance of the cAMP system within cells can be derived from measurement of the kinetics of the incorporation of lsO from water into the a-phospho groups of AMP, ADP, and ATP. This incorporation will result from hydrolysis of cAMP by the phosphodiesterases that allow relaxation to a low cAMP level (Eq. 11-8). It is thought that in human blood platelets this represents the major pathway of this labeling (Eq. 11-9), which occurs at a rate of about 1.1 prnol of lsO kg s . [Pg.556]

Attachment of phosphopantetheine to proteins is catalyzed by a phosphotransferase that utilizes CoA as the donor. A phosphodiesterase removes the phosphopantetheine, providing a turnover cycle.15, 5b A variety of synthetic analogs have been made.4 16 The reactive center of CoA and phosphopantetheine is the SH group, which is carried on a flexible arm that consists in part of the (3-alanine portion of pantothenic acid. A mystery is why pantoic acid, a small odd-shaped molecule that the human body cannot make, is so essential for life. The hydroxyl group is a potential reactive site and the two methyl groups may enter into formation of a "trialkyl lock" (p. 485), part of a sophisticated "elbow" or shoulder for the SH-bearing arm. [Pg.723]

A) Inhibition of platelet phosphodiesterases (PDEs) [91]. Quercetin and myricetin potentiated the anti-aggregatory action of prostacyclin (PGI2), a potent stimulator of platelet adenylate cyclase synthesised by the vascular endothelium, on ADP-induced platelet aggregation in washed human platelets, and the elevation of platelet cyclic adenosine monophosphate (cAMP) elicited by PGI2 [89,92,93]. These effects are probably due to an inhibition of PDEs. As suggested by Ferrell and co-workers [92], this inhibition arises from the similarity between the pyranone ring of flavonoids and the pyrimidine ring of adenine. [Pg.581]

The various compounds were tested in the routine assay under all of the conditions noted in Table IV liberation of Pi after incubation with large excesses of purified enzyme was not detected. Compounds of groups (2) and (3), containing phosphodiester or internal phosphoanhydride linkages, were additionally tested with human semen phosphomonoesterase after incubation with E. coli pyrophosphatase. No Pi was liberated after this dual incubation, indicating absence of phosphodiesterase or coenzyme-degrading activity in the pyrophosphatase (12). [Pg.521]


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See also in sourсe #XX -- [ Pg.70 ]




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