Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nimesulide, the prototype of a new class of anti-inflammatory drugs, dose-dependently decreases the production of the superoxide anion (O2-.) in N-formyl-methionyl-leucyl-phenylalanine (fMLP)- and in phorbol myristate acetate (PMA)-stimulated polymorphonuclear leukocytes. The inhibition of O2-. is possibly related to its inhibitory effect on polymorphonuclear leukocyte cytosolic phosphodiesterase type IV (IC50 = 39 +/- 2 microM), to the related increase in cAMP (P < 0.01 at 1 microM) and the subsequent increase in protein kinase A activity. In fact H-89, a specific protein kinase A inhibitor, counteracts the inhibitory effect of nimesulide on O2-. production by fMLP and PMA. The activation of protein kinase A may prompt the phosphorylation of a number of substrates, thus inhibiting the assembly of NADPH-oxidase in the plasma membrane. Accordingly, nimesulide decreases PMA-induced assembly of NADPH-oxidase in polymorphonuclear leukocytes plasma membranes by about 35%. Protein kinase A activation may also interfere with chemotaxis. Nimesulide inhibits stimulated chemotaxis and the effect is decreased by H-89. Inhibition of phosphodiesterase type IV may explain many of nimesulide's effects.
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PMID:Nimesulide decreases superoxide production by inhibiting phosphodiesterase type IV. 780 66

Salmeterol is a long-acting beta 2-adrenoceptor agonist, with several antiasthma properties. Nimesulide is a nonsteroidal anti-inflammatory drug, supposed to act by inhibition of phosphodiesterase type IV. This might indicate that the effects of both drugs are mediated by an increase in cyclic adenosine monophosphate (cAMP). For salmeterol, it has been shown that it inhibits the influx of eosinophils into the lungs of guinea-pigs after platelet-activating factor (PAF) challenge, suggesting an effect of cAMP on eosinophil migration. For neutrophils, it has been shown that PAF synthesis is inhibited by cAMP. In the present study, we have, therefore, measured the effect of salmeterol and nimesulide on two important human eosinophil functions: chemotaxis; and synthesis of PAF and leukotriene C4 (LTC4). Both drugs were found to be inhibitors of the chemotactic responses of human eosinophils. However, at comparable concentrations, only nimesulide was able to inhibit the synthesis of PAF and LTC4 in activated eosinophils. These results indicate that although the effects of both drugs are thought to be mediated by an increase in cyclic adenosine monophosphate, they have differential effects on eosinophil chemotaxis and synthesis of lipid mediators.
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PMID:The effect of salmeterol and nimesulide on chemotaxis and synthesis of PAF and LTC4 by human eosinophils. 887 Oct 60

The aim of the present study was to investigate the role of phosphodiesterase (PDE) enzyme inhibitors namely rolipram and theophylline in pain and inflammation in experimental animals. Rolipram, a selective PDE IV inhibitor and theophylline a nonspecific PDE inhibitor exerted dose dependent analgesic and anti-inflammatory effect against acetic acid-induced writhing in mice and carrageenan-induced paw edema in rats, respectively. Nimesulide (1, 2 mg/kg) produced significant anti-inflammatory effect. Further, nimesulide (0.5 mg/kg) potentiated analgesic effect of rolipram but it failed to modulate the anti-inflammatory effect of PDE inhibitors. Present study suggests that PDE enzymes might be playing a role in nociceptive and inflammatory responses in animals.
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PMID:Analgesic and anti-inflammatory effects of phosphodiesterase inhibitors. 1123 80