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Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Plasma membranes from ascites hepatoma cells (AH-7974, AH-130) contained much smaller amounts of calmodulin (about half) and cyclic AMP phosphodiesterase (about one-third) compared to plasma membranes of rat livers. 2. Some of calmodulin molecules in liver plasma membranes were released by repeated washing. The 'washed' liver plasma membranes showed the presence of specific binding sites for externally added calmodulin molecules (bovine brain) (N = 140 pmol/mg protein, Kd = 7.9 . 10(-8) M). The calmodulin content of AH-7974 plasma membranes was not reduced by repeated washing. The binding of calmodulin to the 'washed' AH-7974 plasma membranes was only of nonspecific nature with negative cooperativity. 3. Plasma membranes (liver and AH-7974) appeared to contain both calmodulin-dependent and calmodulin-independent phosphodiesterase, but the stimulation by externally added Ca2+ plus calmodulin was rather small. Externally added calmodulin-dependent phosphodiesterase (bovine brain) was bound more to 'washed' liver plasma membranes than to 'washed' AH-7974 plasma membranes. Newly bound phosphodiesterase appeared to be more sensitive to the stimulation by Ca2+ plus calmodulin in 'washed' hepatoma plasma membranes than in 'washed' liver plasma membranes. 4. Preincubation of 'washed' plasma membranes (liver and hepatoma) with calmodulin did not affect the binding of phosphodiesterase, but the sensitivity of phosphodiesterase to the stimulation by Ca2+ plus calmodulin in hepatoma plasma membranes was lost.
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PMID:Dynamics of calmodulin and cyclic AMP phosphodiesterase in plasma membranes of rat livers and ascites hepatomas. 627 Dec 50

Cyclic nucleotide phosphodiesterase activities (3',5'-cyclic nucleotide 5'-nucleotidohydrolase, EC 3.1.4.17) were found in the 40,000 X g supernatant fraction of homogenates of Xenopus laevis oocytes. In the supernatant, the ratio of the specific activity of cyclic AMP phosphodiesterase to that of cyclic GMP phosphodiesterase was 1.1 at the 1 micro substrate level. Two phosphodiesterase forms were isolated by centrifugation on sucrose gradient: a 3-4 S form hydrolyzing specificity cyclic AMP and a 6-7 S form hydrolyzing both cyclic nucleotides (cyclic AMP and cyclic GMP). The activity of the 6-7 S phosphodiesterase was characterized by its activation by 0.1 micro M calmodulin purified from beef pancreas in the presence of 50 micro M CA2+. The calmodulin dependence of this form was completely abolished in the presence of 1 mM ethyleneglycobis(beta-aminoethyl ether)-N-N,N',N'-tetraacetic acid (EGTA). Trifluoperazine at 0.1 mM inhibited both the freshly prepared crude enzyme and the partially purified 6-7 S form. On the other hand, no effect of cyclic GMP at 3 micro M was observed on cyclic AMP hydrolysis in the case of the supernatant or that of the partially purified phosphodiesterases. These data show the presence of a calmodulin-dependent phosphodiesterase in the soluble fraction of X. laevis oocytes.
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PMID:Characterization of the soluble cyclic nucleotide phosphodiesterases in Xenopus laevis oocytes. Evidence for a calmodulin-dependent enzyme. 628 Jul 70

A model for the activation of phosphodiesterase by calmodulin based on a conversion of inactive dimers to active monomers, derived from radiation inactivation studies J. Biol. Chem. (1981) 256, 11351-11355 has been re-examined using a simple probability argument. We conclude that the original model is not supported by the radiation inactivation studies, since our analysis of this model would predict that the rate of radiation inactivation of calmodulin-dependent phosphodiesterase activity be exactly twice that for the decay in total activity in marked contrast with the results obtained.
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PMID:The substructure of phosphodiesterase as established by radiation inactivation. A reinterpretation of results. 629 77

We have isolated two Ca2+-binding proteins from squid optic lobes, each of which is also able to bind phenothiazines in a Ca2+-dependent manner. These proteins have each been purified and partly characterized. One of the proteins corresponds to calmodulin, in that it has a similar amino acid content to bovine brain calmodulin, including a single residue of trimethyl-lysine, it co-migrates with bovine calmodulin both on alkaline-urea- and on sodium dodecyl sulphate (SDS)/polyacrylamide-gel electrophoresis, and will activate calmodulin-dependent phosphodiesterase. The second protein has the same subunit molecular weight as calmodulin, as determined by SDS/polyacrylamide-gel electrophoresis, Mr 17 000, but migrates more slowly than this protein on alkaline-urea-gel electrophoresis. It has an amino acid composition distinct from calmodulin, containing no trimethyl-lysine, its CNBr fragments migrate on alkaline gels in a pattern distinct from those of calmodulin and it shows little ability to activate phosphodiesterase. The u.v.-absorption spectra of the proteins indicate the absence of tryptophan and the presence of a high phenylalanine/tyrosine ratio in each. Both proteins also bind 3-4 calcium ions/mol at 0.1 mM-free Ca2+ and each binds chlorpromazine in a Ca2+-dependent manner.
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PMID:Two low-molecular-weight Ca2+-binding proteins isolated from squid optic lobe by phenothiazine--Sepharose affinity chromatography. 630 66

Carboxylmethylation of several preparations of cAMP phosphodiesterase by the enzyme protein O- carboxylmethyltransferase and S-adenosylmethionine reduces the extent to which the enzyme was activated by native calmodulin. In contrast, carboxylmethylation of calmodulin produced only a slight reduction in the ability of calmodulin to activate cAMP phosphodiesterase. The effect of carboxylmethylation of calmodulin was most prominent at subsaturating calmodulin concentrations, whereas the reduction in the activation of carboxylmethylated cAMP phosphodiesterase was independent of calmodulin concentration. Kinetics and stoichiometric analysis of calmodulin carboxylmethylation indicated that less than 5% of calmodulin was methylated and that the Km of protein O- carboxylmethyltransferase for calmodulin was approximately 350 microM. The extent of calmodulin carboxylmethylation was not affected by either EGTA or Ca2+. When homogeneous bovine brain phosphodiesterase was carboxylmethylated , a rapid decrease in calmodulin-induced stimulation was noted, occurring within 30 s of incubation. Acidic sodium dodecyl sulfate-gel electrophoresis of bovine brain phosphodiesterase revealed a major band of 60,000 daltons which contained radio-activity after carboxylmethylation . Stoichiometric analysis revealed that approximately 20% of the phosphodiesterase was carboxylmethylated . Thus, although calmodulin can serve as a substrate for carboxylmethylation , it appears that carboxylmethylation has a greater effect on calmodulin-dependent phosphodiesterase activity when the target enzyme, rather than calmodulin, is carboxylmethylated .
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PMID:Carboxylmethylation of phosphodiesterase attenuates its activation by ca2+-calmodulin. 632 88

The pharmacological effects of N-[2-(4-(benzhydryloxy)piperidino)ethyl]-3-hydroxy-5-(3-pyridyl methoxy)-2- naphthamide (F-1322), a novel anti-asthmatic agent, was investigated in vitro. The results obtained were as follows: 1) In the isolated trachea of guinea pigs, F-1322 showed a markedly potent antagonistic action against the contraction induced by histamine, while it had little or no effect on 5-hydroxytryptamine-, acetylcholine-, leukotriene D4- or U-46619-induced contractions. 2) In rabbit platelets, F-1322 did not affect the platelet aggregation induced by platelet activating factor. 3) F-1322 significantly inhibited the thromboxane (TX) A2 synthetase (IC50 value: 1.7 x 10(-8) M) and 5-lipoxygenase (IC50 value: 9 x 10(-7) M) activities. 4) F-1322 had no effect on phospholipase A2, cyclooxygenase, Ca2+/calmodulin-dependent phosphodiesterase and phosphodiesterase activities. These in vitro studies suggest that the anti-asthmatic action of F-1322 is associated with histamine antagonism and an inhibitory action on TXA2 synthetase and 5-lipoxygenase activities.
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PMID:[Pharmacological profiles of F-1322, a novel anti-asthmatic agent. (1). Mechanisms of action]. 759 May 21

The second messenger molecules cAMP and Ca2+ regulate a large number of eukaryotic cellular events. cAMP acts on protein kinases, and Ca2+ works through a ubiquitous calcium-binding protein, calmodulin. The 2 systems are not independent, however, but interact in several important fashions. These interactions can be demonstrated by calmodulin-dependent phosphodiesterase. The bovine heart calmodulin-dependent phosphodiesterase can be phosphorylated by cAMP-dependent protein kinase, resulting in a decrease in the enzyme's affinity for calmodulin. The phosphorylation of calmodulin-dependent phosphodiesterase is blocked by Ca2+ and calmodulin, and reversed by the calmodulin-dependent phosphatase (calcineurin). The dephosphorylation is accompanied by an increase in the affinity of the phosphodiesterase for calmodulin. Results from this study suggest that the activity of this phosphodiesterase is precisely regulated by cross-talk between Ca2+ and cAMP signalling pathways.
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PMID:Molecular interaction between cAMP and calcium in calmodulin-dependent cyclic nucleotide phosphodiesterase system. 798

Two forms of phosphodiesterase (F1 and F2) with different regulatory properties have been isolated from the soluble fraction of human brain cortex. F1 is the Ca(2+)-calmodulin-dependent phosphodiesterase and its activity is inhibited by calmodulin antagonists (W-7, TFP, tamoxifen) via a mechanism typical for the majority of Ca(2+)-calmodulin-dependent enzymes. F2 is activated by micromolar concentrations of cGMP (7-14-fold) and by Ca2+ ions (1.5-3-fold) in the absence of exogenous calmodulin. F2 contains a tightly bound Ca(2+)-binding component (apparently calmodulin) which does not dissociate from the enzyme in the presence of EGTA. The mechanism of calmodulin antagonists action on F2 is different from that for F1.
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PMID:[Ca2+-dependent regulation of cGMP-stimulated phosphodiesterase from the soluble fraction of the human brain]. 807 51

Bovine brain contains two calmodulin-dependent phosphodiesterase kinases which are separated on Sephacryl S-300 column. One of these kinases has been purified to homogeneity and shown to belong to the calmodulin-dependent protein kinase II family. Phosphorylation of the 63 kDa phosphodiesterase by this purified protein kinase results in the incorporation of 1.0 mol phosphate per mol subunit and an accompanying increase in Ca2+ concentrations required for the phosphodiesterase activation by calmodulin. The protein kinase undergoes autophosphorylation to incorporate 1.0 mol phosphate per mol of subunit of the enzyme and the autophosphorylated enzyme is active, independent of the presence of Ca2+. The autophosphorylation reaction as well as the protein kinase reaction are rendered Ca2+ independent in less than 15 seconds when approximately one mol phosphate per mol protein kinase is incorporated. The result suggests that activation of phosphodiesterase phosphorylation reaction may occur prior to the activation of phosphodiesterase and phosphatase during a cell Ca2+ flux via the protein kinase autophosphorylation mechanism.
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PMID:Purification and characterization of bovine brain calmodulin-dependent protein kinase. II. The significance of autophosphorylation in the regulation of 63 kDa calmodulin-dependent cyclic nucleotide phosphodiesterase isozyme. 823 47

The effects of various ginsenosides on calmodulin-dependent phosphodiesterase isozymes have been investigated. Ginsenosides were found to be potent inhibitors of bovine heart calmodulin-dependent phosphodiesterase and the 60-kDa isozyme of bovine brain calmodulin-dependent phosphodiesterase but not of the 63-kDa isozyme of bovine brain calmodulin-dependent phosphodiesterase. Since the inhibition of phosphodiesterase by ginsenosides was overcome by increasing the concentration of calmodulin, this suggests that ginsenosides act specifically and reversibly against the action of the calmodulin. These compounds therefore should be valuable tools to investigate the diverse physiological roles of distinct phosphodiesterase isozymes.
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PMID:Ginsenosides are potent and selective inhibitors of some calmodulin-dependent phosphodiesterase isozymes. 838 50


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