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)

Using DEAE-cellulose chromatography and Agarose gel filtration we have partially purified a low Km cyclic adenosine monophosphate (AMP) phosphodiesterase from the 100,000 X g supernatant of rat kidneys. The characteristics of this enzyme included a Km of approximately 4 muM a pH optimum of around 8.0 and a requirement for magnesium. This preparation should be suitable for investigation of possible effects of hormones, drugs and cellular constituents on the cyclic AMP pathway through any direct effects on the low Km enzyme. We have also demonstrated a nonspecific, high Km cyclic nucleotide phosphodiesterase and possibly a specific cyclic guanosine monophosphate (GMP) phosphodiesterase in the soluble fraction from rat kidneys.
 ...
PMID:Multiple cyclic nucleotide phosphodiesterases in rat kidney. 0 May 37

The activities of adenylate and guanylate cyclase and cyclic nucleotide 3':5'-phosphodiesterase were determined during the aggregation of human blood platelets with thrombin, ADP, arachidonic acid and epinephrine. The activity of guanylate cyclase is altered to a much larger degree than adenylate cyclase, while cyclic nucleotide phosphodiesterease activity remains unchanged. During the early phases of thrombin-and ADP-induced platelet aggregation a marked activation of the guanylate cyclase occurs whereas aggregation induced by arachidonic acid or epinephrine results in a rapid diminution of this activity. In all four cases, the adenylate cyclase activity is only slightly decreased when examined under identical conditions. Platelet aggregation induced by a wide variety of aggregating agents including collagen and platelet isoantibodies results in the "release" of only small amounts (1-3%) of guanylate cyclase and cyclic nucleotide phosphodiesterase and no adenylate cyclase. The guanylate cyclase and cyclic nucleotide phosphodiesterase activities are associated almost entirely with the soluble cytoplasmic fraction of the platelet, while the adenylate cyclase if found exclusively in a membrane bound form. ADP and epinephrine moderately inhibit guanylate and adenylate cyclase in subcellular preparations, while arachidonic and other unsaturated fatty acids moderately stimulate (2-4-fold) the former. It is concluded that (1) the activity of platelet guanylate cyclase during aggregation depends on the nature and mode of action of the inducing agent, (2) the activity of the membrnae adenylate cyclase during aggregation is independent of the aggregating agent and is associated with a reduction of activity and (3) cyclic nucleotide phosphodiesterase remains unchanged during the process of platelet aggregation and release. Furthermore, these observations suggest a role for unsaturated fatty acids in the control of intracellular cyclic GMP levels.
 ...
PMID:Cyclic nucleotides and platelet aggregation. Effect of aggregating agents on the activity of cyclic nucleotide-metabolizing enzymes. 0 49

3',5'-Cyclic-AMP 5'-nucleotidohydrolase (cAMP phosphodiesterase, EC 3.1.4.17) was partial purified from metacercariae of Paragonimus africanus. The enzyme activity absolutely depends on Mg2 or Mn2+. The pH-optimum of the cAMP phosphidiesterase was found at pH 8.0. The Michaelis constant for cAMP was determined to be 5 X 10(-6) M. Papaverine deoxyadenosine, theophylline and adenosine were found to be competitive inhibitors of the enzyme activity. The inhibitor constants were calculated to be 13 X 10(-6)M, 25 X 10(-5)M, and 35 X 10(-5)M, and 85 X 10(-5)M,respectively. The molecular weight of the cAMP phosphodiesterase was estimated to be about 40 000 by gel filtration.
 ...
PMID:Properties of 3',5'-cyclic-AMP phosphodiesterase from Paragonimus africanus metacercariae. 1 Jun 55

Two soluble forms of 3':5'-cyclic-nucleotide phosphodiesterase (o':5'-cyclic-nucleotide 5'-nucleotidohydrolase, EC 3.1.4.17) were found in the larval fat body of the silkmoth Hyalophora cecropia. These differ in elution profile on Sephadex G-200, solubility in ammonium sulfate, metal ion requirements and kinetic properties. Phosphodiesterase I has Km values of 11 muM and 1.8 muM for cyclic AMP and cyclic GMP, respectively, has 5-fold greater maximal activity with cyclic AMP than with cyclic GMP, and is activated by Mg2+ and Co2+, and inhibited by EDTA. phosphodiesterase II has Km values of 625 muM and 125 muM for cyclic AMP and cyclic GMP, respectively, has similar maximal activity with both substrates, and is not activated by divalent metal ions or inhibited by EDTA. Cyclic nucleotides and methylxanthines competitively inhibit both enzymes. Phosphodiesterase is found in both soluble and particulate fractions of homogenates. Total activity is highest during the larval stage of the insect, drops markedly following pupation, and rises again during pharate adult development.
 ...
PMID:Cyclic nucleotide phosphodiesterases of Hyalophora cecropia silkmoth fat body. 1 89

The activity of 2-bromo-alpha-ergokryptine (bromocriptine) (5 mg kg-1, i.p.) on adenylate cyclase and on phosphodiesterase (PDE-PDE II) of rat striatum, has been examined both in vitro and in vivo. In vitro and in vivo bromocriptine stimulated adenylate cyclase activity, but reduced the stimulating effect of dopamine on adenylate cyclase activity. Bromocriptine showed a dose-dependent biphasic action on phosphodiesterases in vitro while in vivo it stimulated them. The results obtained proved bromocriptine to have an agonist-antagonist action at striatal dopamine receptor level, with a relevant effect on the cAMP system.
 ...
PMID:Effects of bromocriptine on adenylate cyclase and phosphodiesterase activities of rat striatum. 2 11

Thermostable protein fraction from retina of rats with hereditary retinal dystrophy (Hunter and Campbell strains) did not inhibit cyclic nucleotide phosphodiesterase. At the same time an inhibitory component, found in retina of Wistar rat, rabbit, frog and lamprey, was similar to the component from bovine retina. Quantity of the inhibitory component in normal rat retina decreased considerably within postnatal period (12 days--3 months). Thermostable proteins, isolated from Campbell rat retina, differed from that of Hunters' one by electrophoretic properties while both preparations were dissimilar to the protein of normal rat. Protein bands, containing inhibitory component from dystrophic rat retina, appear to be less distinct as compared to those of normal rat. These proteins, eluated from the bands of Campbell rats, activated phosphodiesterase but the preparations from Hunter rats did not influence on it.
 ...
PMID:[Protein inhibitor of cyclic nucleotide phosphodiesterase in the retina in hereditary degeneration]. 2 6

Various receptor-linked cyclic AMP systems were measured in rat neostriatum 2--14 days after selective destruction of neuronal cell bodies and dendrites by micro-injection of 3 microgram of kainic acid. Basal adenylate cyclase activity was reduced by up to 56% in the injected side and the sensitivity to dopamine was abolished. Up to 84% of cyclic nucleotide phosphodiesterase activity, hydrolyzing either cyclic AMP or cyclic GMP, was destroyed by kainic acid injection. Specific binding of [3H]etorphine and [3H]spiroperidol was reduced by up to 62% in the injected side, while non-specific binding was unchanged. All of these changes were time-dependent, and were greatest 7--14 days after kainic acid treatment. On the other hand, intrastriatal kainic acid injection caused no change in the steady-state concentration of cyclic AMP in striatal slices, or in the in vivo cyclic AMP content in the striatum of rats killed by microwave irradiation. Receptor-mediated increases in cyclic AMP accumulation in striatal slices were either unchanged or markedly potentiated by kainic acid treatment. The maximum response to adenosine was unchanged, while the response to isoprenaline was increased up to 3.7-fold, the response to dopamine increased up to 6.7-fold, and the response to PGE1 increased up to 30-fold. The effect of dopamine in kainic acid-treated striatal slices was no longer blocked by fluphenazine, but was blocked by propranolol, suggesting an interaction of dopamine with a beta-adrenoceptor in kainic acid-treated slices. The results suggest differential cellular localizations of the various receptor-linked cyclic AMP systems in rat neostriatum. Some dopamine and opiate receptors, as well as most of the phosphodiesterase activity, are associated with local neuronal elements, while beta-adrenoceptor, adenosine and PGE1 alterations in cyclic AMP are not. The potentiation of the beta-adrenoceptor and PGE1 responses suggests that they may occur in glial cells. In addition, the pool of adenylate cyclase destroyed by kainic acid appears to make little contribution to normal levels of cyclic AMP in the tissue.
 ...
PMID:Receptor-linked cyclic AMP systems in rat neostriatum: differential localization revealed by kainic acid injection. 2 87

[3H]Spiperone binding sites and the dopamine-sensitive adenylate cyclase were measured in rat substantia nigra (s. nigra) 7 or 14 days after various lesions. Hemisections, which resulted in a 66% decline in tyrosine hydroxylase and cyclic nucleotide phosphodiesterase and a 73% decrease in glutamate decarboxylase, led to a 50% decrease in [3H]spiperone binding and to the almost complete disappearance of the dopamine-sensitive adenylate cyclase from the s. nigra on the lesioned side. 6-Hydroxydopamine injection into the s. nigra, which depleted tyrosine hydroxylase activity within the s. nigra by 85%, while leaving phosphodiesterase unaffected, resulted in a 40% decrease in [3H]spiperone binding but no change in the dopamine-sensitive adenylate cyclase. Intrastriatal injections of kainic acid did not alter tyrosine hydroxylase activity in the s. nigra, but decreased both glutamate decarboxylase (54%) and phosphodiesterase (68%); [3H]spiperone binding was unaffected by this lesion while the dopamine-sensitive adenylate cyclase was greatly reduced (50-75%). These results suggest that within the s. nigra the dopamine receptor binding sites as defined using [3H]spiperone are located on dopamine neurones while the dopamine-sensitive adenylate cyclase is located presynaptically on striatonigral nerve terminals.
 ...
PMID:Dissociation between the presynaptic dopamine-sensitive adenylate cyclase and [3H]spiperone binding sites in rat substantia nigra. 3 4

As revealed by spectrophotometry, native but not heat-inactivated influenza virus in the presence of ATP reduced the activity of calcium-dependent regulator protein-stimulated 3',5'-c AMP-phosphodiesterase (CDR-PDE). ATP could be partially replaced by ADP but not by AMP. The degree of CDR-PDE inhibition increased with increasing virus concentration. But at very high virus concentrations the rate of 3',5'-c AMP hydrolysis by CDR-PDE was not linearly dependent on time. At appropriate virus concentrations the degree of inhibition of CDR-PDE activity remained unchanged for the whole reaction time.
 ...
PMID:Role of calcium-dependent regulator protein (CDR) in inhibition of 3',5'-c AMP-phosphodiesterase by influenza virus. II. Kinetic studies on inhibition of CDR-dependent phosphodiesterase by influenza virus. 4 Apr 17

Adenyl cyclase (AC) and cyclic nucleotide phosphodiesterase (PDE) have been studied in muscle from patients affected with muscular and neuromuscular diseases as well as in muscle of rats after experimental denervation. A diminution of AC was observed in Duchenne's dystrophy, in neurogenic atrophies, in inflammatory forms, in myasthenia and myotonia. PDE was diminished in Duchenne's dystrophy and increased in all other diseases considered. Both enzymes were increased in rat muscle after nerve transection. The possible mechanism underlying the biochemical alterations observed are discussed including unmasking of extra-activity due to changed metabolic environment, tissue destruction and activation of lysosomal activity.
 ...
PMID:The metabolism of cyclic-3'-5'-adenosine monophosphate (cAMP) in diseased muscle. 5 Apr 11


1 2 3 4 5 6 7 8 9 10 Next >>