Disease relevance of PDE3A

• There are reports of serious hypotension or circulatory shock when sildenafil citrate, a selective cyclic nucleotide phosphodiesterase type 5 inhibitor, which was developed for the treatment of erectile dysfunction, is given to patients taking certain coronary vasodilators [1].
• Arrhythmias were induced by 8-Br-cAMP (5 X 10(-2) M) in the presence of inhibitor of cyclic nucleotide phosphodiesterase (3 X 10(-4) M Ro 7-2956) within 30 min [2].

High impact information on PDE3A

• The factor was identified by acrylamide gel electrophoresis and by enzyme activation studies as the Ca2+-binding protein that regulates the activity of a brain cyclic nucleotide phosphodiesterase [3].
• We have identified a new cyclic-nucleotide phosphodiesterase isoform, PDE3A, and cloned its cDNA from cultured aortic myocytes [4].
• Identification of a novel isoform of the cyclic-nucleotide phosphodiesterase PDE3A expressed in vascular smooth-muscle myocytes [4].
• Identification and function of cyclic nucleotide phosphodiesterase isoenzymes in airway epithelial cells [5].
• PURPOSE: To characterize cyclic nucleotide phosphodiesterase isozyme activities in human trabecular meshwork cells and primary cultures of porcine trabecular meshwork cells [6].

Biological context of PDE3A

• The structure-activity relationships of a series of 4,5-dihydro-6-[4-(1H-imidazol-1-yl)phenyl]-3(2H)-pyridazinones and related compounds were investigated for the in vivo inhibition of different forms of cyclic nucleotide phosphodiesterase (PDE) isolated from guinea pig ventricular muscle [7].
• Phosphorylation of calmodulin on serine/threonine residues by casein kinase II decreases its ability to activate both myosin-light-chain kinase and cyclic nucleotide phosphodiesterase [8].
• Specific cyclic nucleotide phosphodiesterase inhibitors differently modulate contractile kinetics in airway smooth muscle [9].
• The cyclic nucleotide phosphodiesterase (PDE) inhibitor milrinone, a PDE 3-inhibitor with an IC50 2.4 +/- 1.8 mumol/L, (n = 6) was 10 times more potent than rolipram (PDE 4-inhibitor), zaprinast (PDE 5-inhibitor) and vinpocentine (PDE 1-inhibitor) [10].

Anatomical context of PDE3A

• Inhibition of separated forms of cyclic nucleotide phosphodiesterase from pig coronary arteries by 1,3-disubstituted and 1,3,8-trisubstituted xanthines [11].
• Cardiotonic agents. 7. Inhibition of separated forms of cyclic nucleotide phosphodiesterase from guinea pig cardiac muscle by 4,5-dihydro-6-[4-(1H-imidazol-1-yl)phenyl]-3(2H)-pyridazinones and related compounds. Structure-activity relationships and correlation with in vivo positive inotropic activity [7].
• Two cyclic nucleotide phosphodiesterase (PDE) activities were identified in pig aortic endothelial cells, a cyclic GMP-stimulated PDE and a cyclic AMP PDE [12].
• Multiple molecular forms of cyclic nucleotide phosphodiesterase in cardiac and smooth muscle and in platelets. Isolation, characterization, and effects of various reference phosphodiesterase inhibitors and cardiotonic agents [13].
• Pulmonary effects of seven xanthines, exhibiting a range of potencies as cyclic nucleotide phosphodiesterase (PDE) inhibitors and as adenosine antagonists, were investigated in anesthetized and ventilated guinea pigs [14].

Associations of PDE3A with chemical compounds

• This effect was markedly potentiated by the cyclic nucleotide phosphodiesterase inhibitor theophylline [15].
• A series of 7-substituted 1-methyl-3-isobutylxanthines was designed in an attempt to increade the specificity of the 1-methyl-3-isobutylxanthine (MIX) structure for one of the two cyclic nucleotide phosphodiesterase peaks isolated by DEAE-cellulose chromatography of the soluble fraction of the intima + media layer of pig coronary arteries [16].
• The effectiveness of theophylline (aminophylline) in treating asthma may result in part from nonselective inhibition of multiple isozymes of cyclic nucleotide phosphodiesterase (PDE) [17].
• The interactions of psychotropic drugs with phospholipids, including lysophosphatidylcholine, phosphatidylinositol, and lysophosphatidylserine, were studied using calmodulin-dependent cyclic nucleotide phosphodiesterase partially purified from the cortex of hog brain [18].
• Calcium-dependent cyclic nucleotide phosphodiesterase from brain: comparison of adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate as substrates [19].

Regulatory relationships of PDE3A

• Benzylisoquinoline compounds inhibit the ability of calmodulin to activate cyclic nucleotide phosphodiesterase [20].
• These findings indicate that Ro 20-1724 and IBMX augment the action of cholecystokinin on enzyme secretion by inhibiting cyclic nucleotide phosphodiesterase and allowing a significant cholecystokinin-induced increase in cellular cAMP [21].

Other interactions of PDE3A

• Differences in the association of calmodulin with cyclic nucleotide phosphodiesterase in relaxed and contracted arterial strips [22].
• Effects of inhibitors of cyclic nucleotide phosphodiesterase on actions of cholecystokinin, bombesin, and carbachol on pancreatic acini [21].

References