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...

Insulin stimulation of adipocytes results in serine phosphorylation/activation of phosphodiesterase 3B (PDE 3B) and activation of a kinase that phosphorylates PDE 3B in vitro, key events in the antilipolytic action of this hormone. We have investigated the role for p70 S6 kinase, mitogen-activated protein kinases (MAP kinases), and protein kinase B (PKB) in the insulin signaling pathway leading...

The aim of the present study was to compare the effects of selective phosphodiesterase (PDE) 3, 4 and 5 inhibitors on antigen-induced airway hyperresponsiveness in sensitized guinea-pigs. When the sensitized guinea-pigs were orally pre-treated with the selective PDE4 inhibitor, Ro 20-1724 (30 mg/kg), and studied 48h after OA, a significant reduction (P<0.01) of the leftward shift of the dose-re...

BACKGROUND We have previously shown major differences in beta-adrenergic and muscarinic modulation of L-type calcium currents (ICa) in newborn and adult rabbit heart. However, little is known about developmental changes in modulation of ICa by phosphodiesterases (PDEs), which also regulate intracellular cAMP concentration by its hydrolysis. METHODS AND RESULTS Enzymatically isolated adult and...

The interaction between nitric oxide (NO) and renin is controversial. cAMP is a stimulating messenger for renin, which is degraded by phosphodiesterase (PDE)-3. PDE-3 is inhibited by cGMP, whereas PDE-5 degrades cGMP. We hypothesized that if endogenous cGMP was increased by inhibiting PDE-5, it could inhibit PDE-3, increasing endogenous cAMP, and thereby stimulate renin. We used the selective P...

BACKGROUND Resveratrol is a cardioprotective agent with known antiarrhythmic effects that has recently been shown to inhibit phosphodiesterase (PDE) enzyme activity. Thus, it is possible that resveratrol increases the inotropic effect of sympathomimetic agents, as PDE inhibitors do but, unlike other PDE inhibitors, its effect may not be accompanied by proarrhythmia due to its antiarrhythmic act...

Platelets contain two cAMP phosphodiesterases (PDEs) which regulate intracellular cAMP levels, cGMP-inhibited cAMP PDE (PDE3A) and cGMP-stimulated PDE (PDE2A). Using the PDE3 inhibitor, milrinone and the PDE2 inhibitor, erythro-9-(2-hydroxyl-3-nonyl)adenine (EHNA), we have explored the contribution of each PDE to the regulation of platelet function. Inhibition of PDE2 resulted in higher levels ...

Though antiplatelet drugs are proven beneficial to patients with coronary heart disease and stroke, more effective and safer antiplatelet drugs are still needed. In this study we report the antiplatelet effects and mechanism of BF0801, a novel adenine derivative. BF0801 dramatically inhibited platelet aggregation and ATP release induced by ADP, 2MeSADP, AYPGKF, SFLLRN or convulxin without affec...

Theophylline, a drug known to inhibit several classes of adenosine 3'5' cyclic monophosphate (cAMP) phosphodiesterases (PDEs), induces apoptosis in chronic lymphocytic leukemia (CLL) cells. Because the PDE target for theophylline in CLL remains unknown, we examined the ability of isoform-specific PDE inhibitors to increase cAMP levels and induce apoptosis in primary CLL cells. Reverse transcrip...

Because phosphodiesterase (PDE) expression and activity are controlled by cAMP, we investigated whether activating mutations of Gs alpha gene that occur in human GH-secreting adenomas are associated with increased PDE activity. We studied 10 adenomas with wild-type Gs alpha (gsp-) and 8 with mutant Gs alpha (gsp+). Although, in the absence of PDE inhibitors, intracellular cAMP levels were simil...