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)

An inhibitor of cyclic adenosine 3',5'-monophosphate (cAMP) phosphodiesterase was isolated from the culture filtrate of Bacillus subtilis C-756 isolated from soil. It was purified and finally separated into three fractions by reverse-phase HPLC. The respective fractions were designated as APD-I, -II and -III in the order eluted and the relative quantities of APD-I, -II and -III were approximately 10%, 40% and 50%, respectively. They were acylpeptides composed of beta-hydroxy fatty acid residues and heptapeptide. Though the amino acid compositions of the peptides were the same, the fatty acid residues were all different. APD-I contained a mixture of 3-hydroxy-11-methyldodecanoic acid (i-C13h3) and 3-hydroxy-10-methyldodecanoic acid (a-C13h3). APD-II contained 3-hydroxytetradecanoic acid (n-C14h3). APD-III contained a mixture of 3-hydroxy-13-methyltetradecanoic acid (i-C15h3) and 3-hydroxy-12-methyltetradecanoic acid (a-C15h3).
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PMID:Acylpeptides, the inhibitors of cyclic adenosine 3',5'-monophosphate phosphodiesterase. I. Purification, physicochemical properties and structures of fatty acid residues. 630 57

Acylpeptides, APD-I, -II and -III, were inhibitors of cyclic adenosine 3',5'-monophosphate (cAMP) phosphodiesterase, and their inhibition types were non-competitive. The inhibitory activity of APD-II was the most potent among them. Opening of the lactone linkage reduced the inhibitory activity to about half. The activity almost disappeared when an inhibitor or a derivative with opened lactone linkage was methylated with diazomethane. The activity was, however, restored by the addition of metal ions such as Ca2+, Mn2+, Fe2+, and Co2+. This suggests that the inhibition may be caused by a chelating action of the free carboxyl groups of glutamic acid and aspartic acid in the peptide.
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PMID:Acylpeptides, the inhibitors of cyclic adenosine 3',5'-monophosphate phosphodiesterase. III. Inhibition of cyclic AMP phosphodiesterase. 630 59

Much evidence indicates that increased persistent sodium current (I(Na.P)) is associated with cellular calcium overload and I(Na.P) is considered to be a potential target for therapeutic intervention in ischaemia and heart failure. By inhibiting type III phosphodiesterase, milrinone increases intracellular cyclic adenosine monophosphate (cAMP), with a positive inotropic effect. However, the effect of milrinone on increased I(Na.P) under pathological conditions remains unknown. Accordingly, we investigated the effect of milrinone on increased I(Na.P) induced by hypoxia or hydrogen dioxide in guinea pig ventricular myocytes. While milrinone (0.01 mM or 0.1mM) or cAMP (0.1 mM) decreased I(Na.P) respectively in control condition, application of 1 microM H-89, a selective cAMP-dependant protein kinase inhibitor, prevented the effect of 0.1mM milrinone in control condition. Milrinone (0.1 mM) reduced the increased I(Na.P) induced by hypoxia. Furthermore, 0.01 mM or 0.1mM milrinone reduced the enhanced I(Na.P) induced by 0.3 mM hydrogen peroxide. In addition, 0.01 mM or 0.1 mM milrinone shortened action potential duration at 90% repolarization (APD(90)). Bath application of 0.3 mM hydrogen dioxide markedly prolonged APD(90), while 2 microM tetrodotoxin (TTX) reversed the prolonged APD(90). In the other two groups, 0.01 mM or 0.1 mM milrinone shortened the prolonged APD(90) induced by 0.3 mM hydrogen peroxide, ultimately 2 microM TTX causing a further decurtation of APD(90). These findings demonstrate that milrinone inhibited I(Na.P) under normal condition, hypoxia or hydrogen dioxide-induced I(Na.P), and the APD(90) prolonged by hydrogen dioxide-induced I(Na.P) in ventricular myocytes, which is associated with the mechanism of milrinone increasing intracellular cAMP.
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PMID:Milrinone inhibits hypoxia or hydrogen dioxide-induced persistent sodium current in ventricular myocytes. 1954 13