A method for assaying a novel phosphodiesterase-4 inhibitor, 2-aryl-7(3',4'-dialkoxyphenyl)-pyrazolo [1,5-alpha] pyrimidine (PDE-310), was developed and validated in rat plasma using liquid chromatography-tandem mass spectrometry (LC-MS-MS). Rat plasma samples were processed by liquid-liquid extraction with ethyl acetate and injected onto the LC-MS-MS system for quantification. PDE-310 and imip...

PURPOSE We previously demonstrated that 350 bp of the human rod cGMP phosphodiesterase beta-subunit (beta-PDE) gene promoter are sufficient to direct high levels of gene expression in human Y-79 retinoblastoma cells in vitro. In this study the cell specificity and expression pattern conferred by the short beta-PDE 5' flanking sequence in vivo were examined. METHODS A construct containing the ...

Background: Phosphodiesterases (PDEs) play a major role in the regulation of cyclic adenosine monophosphate (cAMP)- and cyclic guanosine monophosphate (cGMP)-mediated pathways. Their inhibitors exhibit anti-inflammatory, vasodilatory and antithrombotic effects. Therefore, consumption of foods with PDE-inhibiting potential may possess beneficial influence on the risk of cardiovascular diseases. ...

Essential differences in the degree of papaverine [5 x 10(-5) M]- and theophylline [1 x 10(-3) M]-induced inhibition of cyclic nucleotide phosphodiesterase (PDE) were found in homogenates from different structures of the CNS as well as from different organs of male albino rats. Both inhibitors of PDE showed a mosaic pattern of their inhibitory effects on the enzyme activity of the brain structu...

The possible involvement of phosphodiesterase (PDE) activation in phototransduction was investigated in gecko photoreceptors by comparing the in situ PDE activity with the photoreceptor potential. In the dark, intracellular injection of cGMP into a gecko photoreceptor caused a long-lasting depolarization. An intense light flash given during the depolarization phase repolarized the cell with a s...

BACKGROUND The anti-inflammatory effects of the selective phosphodiesterase (PDE) inhibitors cilostazol (PDE 3), RO 20-1724 (PDE 4) and sildenafil (PDE 5) were examined in a murine model of allergic asthma. These compounds were used alone and in combination to determine any potential synergism, with dexamethasone included as a positive control. METHODS Control and ovalbumin sensitised Balb/C ...

Phosphodiesterases (PDEs) limit vasodilation in response to a variety of signaling cascades by metabolizing the cyclic nucleotides cAMP and cGMP. The objective of this study was to test the hypothesis that NO regulates expression of PDE3A, a cGMP-inhibited PDE. Incubation of rat pulmonary artery smooth muscle cells (rPaSMCs) with the NO-donor compound S-nitroso-glutathione (GSNO) increased PDE3...

Calmodulin (CaM) and the cardiac isoform of troponin C (cTnC) are close structural homologs, but cTnC cannot activate most CaM target enzymes. To investigate structure-function relationships, we constructed a series of CaM.cTnC chimeras and determined their ability to bind Ca2+ and activate CaM target enzymes. Previously, we exchanged domain 1 and found that the chimeras exhibited profoundly im...

Nuclear factor of activated T cell (NFAT)-3 is a member of the transcription factor NFAT family, which has been demonstrated to be responsible for the up-regulation of the pro-inflammatory cytokine tumor necrosis factor (TNF) in the immune system. Our most recent studies have also shown that TNF is able to induce cell transformation in mouse epidermal Cl41 cells by induction of cyclooxygenase-2...