Gene/Protein Disease Symptom Drug Enzyme Compound
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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)

A decrease in the activity of the enzyme cytidine 3',5'-monophosphate (cyclic CMP) phosphodiesterase was noted in the regenerating liver of young rats as early as 8 hours after partial hepatectomy, with a maximum decrease occurring 12 hours after the surgery. In comparison, in old rats which showed a slower liver growth, the maximum decrease in the activity of cyclic CMP phosphodiesterase was smaller and occurred at a much later time (2 days after surgery). A similar decrease in the enzyme activity was observed in the fetal liver of guinea pigs. These findings suggest that regulation of tissue concentration of cyclic CMP may be crucial for the regeneration and development of the liver.
Science 1978 Sep 01
PMID:Cytidine 3',5'-monophosphate phosphodiesterase: decreased activity in the regenerating and developing liver. 21 May 3

We have examined the activity of cyclic AMP phosphodiesterase, cyclic GMP phosphodiesterase and the protein activator of cyclic AMP phosphodiesterase in various anatomic and subcellular fractions of the bovine eye. Cyclic GMP hydrolysis was 1.6--12 times faster than hydrolysis of cyclic AMP in the subcellular fractions of the retina and in the precipitate of the rod outer segment. An opposite pattern was seen in the bovine lens, where the hyrolysis of cyclic AMP occurred 17 and 169 times faster than that of cyclic GMP in the supernatant and precipitate of lens, respectively. The activity of cyclic AMP phosphodiesterase was not affected by ethylene-glycol bis(beta-aminoethylether)-N,N'-tetraacetic acid in any fractions except in the retinal supernatant, suggesting that the phosphodiesterase exists primarily as a Ca2+-independent, activator-independent form. However, the protein activator of cyclic AMP phosphodiesterase existed in all fractions examine. A complex kinetic patternwas observed for both cyclic AMP and cyllic GMP hydrolysis by the 105000 times g lens supernatant. The Michaelis constants for both cyclic AMP (1.3-10(-6) and 9.I-10(-6) M) and cyclic GMP (1.04-10(6) AND 1.22 10(-5) M) appeared to be similar.
Biochim Biophys Acta 1978 Sep 11
PMID:Protein activator of cyclic AMP phosphodiesterase and cyclic nucleotide phosphodiesterase in bovine retina and bovine lens. Activity, subcellular distribution and kinetic parameters. 21 Aug 26

Initial and transient increases in the basal levels of cyclic GMP in the heart were noted prior to cardiac hypertrophy in rats administered isoproterenol. Increased levels of cyclic AMP-phosphodiesterase (in both the soluble and particulate fractions) and stimulatory modulator of cyclic GMP-dependent protein kinase, however, were associated with the progression, or the state, of cardiomegaly, with their levels returning to the control values upon regression of the hypertrophy. The levels of cyclic GMP phosphodiesterase in the soluble fraction were lower, whereas those in the particulate fraction were higher, in the hypertrophied heart than the control. In cardiac hypertrophy, the maximal activity ratio(--cyclic AMP/+cyclic AMP) of cyclic AMP-dependent protein kinase in the incubated minced heart caused by isoproterenol was lower, whereas the concentration of isoproterenol required to increase the activity ratio half-maximally was higher than controls; the reduced responsiveness to the drug, however, was reversed when the hypertrophy regressed. These observations, taken collectively, appear to suggest that the desensitization of the beta-adrenergic mechanism seen in the cardiac hypertrophy produced by repeated administration of isoproterenol is associated with adaptive modifications in certain parameters of the cyclic nucleotide systems.
Biochim Biophys Acta 1978 Sep 06
PMID:Alterations in activities of cyclic nucleotide systems and in beta-adrenergic receptor-mediated activation of cyclic AMP-dependent protein kinase during progression and regression of isoproterenol-induced cardiac hypertrophy. 21 Aug 40

Extracts of vegetative cells of Blastocladiella emersonii contain 5% or less of the cyclic AMP phosphodiesterase activity in zoospore extracts. This difference in activity could be accounted for entirely by an increase in the differential rate of phosphodiesterase synthesis during sporulation, beginning after a lag period of about 60 min and extending for at least an additional 90 min into the 4-h sporulation process. To examine the relation between enzyme synthesis and cyclic nucleotide metabolicm, we determined the substrate specificity of phosphodiesterase synthesized during sporulation and partially purified from zoospores. Zoospore extracts contain two components, separable by gel filtration chromatography, with cyclic AMP phosphodiesterase activity. The larger component accounts for 20% of the total activity and the smaller component for 80%. Both components show essentially an absolute substrate specificity for cyclic AMP among several cyclic purine and cyclic pyrimidine nucleotides tested. Nevertheless, we found no change in the total cyclic AMP content of sporulating cells before, during, or after enzyme activity increased. We speculate that some other component of cyclic AMP metabolism or function limits the rate of cyclic AMP hydrolysis in sporulating cells.
J Bacteriol 1978 Sep
PMID:Induction of cyclic AMP phosphodiesterase in Blastocladiella emersonii and its relation to cyclic AMP metabolism. 21 Nov 17

Gentle homogenization followed by differential and density gradient centrifugation was used to purify line 10 and line 1 guinea pig hepatoma plasma membranes in the form of ghosts. Yields of 15--25% allowed enough membranes to be obtained from a single ascites tumor-bearing animal for immunologic and biochemical studies. Although the plasma membrane marker enzyme (Na+ + k+)atpase was present in normal concentrations in both line 10 and line 1 hepatomas, 5'-nucleotidase was reduced over 100-fold in both tumors and phosphodiesterase I was increased 210-fold in the line 10 hepatomas.
J Natl Cancer Inst 1978 Sep
PMID:Preparation of plasma membranes from line 10 and line 1 guinea pig hepatomas. 21 Dec 44

Cerebral cortical slices from rats were incubated in physiologic saline, and the uptake, release, and K+-stimulated release of norepinephrine were measured. Dibutyryl cyclic AMP, the phosphodiesterase inhibitors aminophylline and papaverine, and adenosine (which stimulates adenyl cyclase) all caused a variable increase in uptake of norepinephrine at concentrations ranging from 10(-7) to 10(-4) M. Prostaglandins E1 and E2 appeared to have no effect on uptake, but this may be because the alcohol required to dissolve them had an inhibitory effect on uptake. None of these compounds appeared to affect basal or K+-stimulated release of norepinephrine. These agents therefore seem to have an effect opposite to that of the tricyclic antidepressants (which inhibit uptake of norepinephrine). Since norepinephrine's postsynaptic effects are usually inhibitory in the cortex, the stimulatory effect of the drugs tested on the presynaptic uptake of norepinephrine may explain the stimulant and epileptogenic effects of these drugs.
Neurology 1978 Sep
PMID:Uptake and release of norepinephrine by slices of rat cerebral cortex: effect of agents that increase cyclic AMP levels. 21 64

As compared to fatty tissue cells of animals with normal pressure, those of SHR rats were found to be characterized by a higher lipolytic response and a larger increase in the cAMP content on exposure to the effect of ACTH. As compared to the controls, adrenalectomized SHR rats had an increased basal cAMP content and an increased lipolytic response of the adipocytes following adrenaline administration. In inhibition of phosphodiesterase in the fatty cells of adrenalectomized rats with normal pressure, the cAMP content grew by 20% as compared to that in SHR rats subjected to the operation. It is suggested that the changes in intracellular distribution of calcium, shown in this model of hypertension, may be the direct cause of the altered sensitivity of the "target" cells to the effect of hormones.
Kardiologiia 1978 Sep
PMID:[Mechanism of the change in adipocyte sensitivity to ACTH and adrenaline in spontaneous genetic hypertesion in rats]. 21 34

Repeated daily administration of the dopamine (DA) agonist bromocriptine (15 mg/kg; s.cut.) to rats led to a time dependent decrease in the in vitro binding of [3H]spiperone to striatal membranes. Kinetic analysis of [3H]spiperone binding after 2 and 7 days of bromocriptine treatment showed a 25-50% reduction in the total number of binding sites with no changein their affinity for spiperone. There was also a decreased accumulation of cyclic AMP (cAMP) in striatal slices in response to DA after bromocriptine treatment. The DA-sensitive adenylate cyclase in striatal homogenates, however, remained unchanged in bromocriptine treated rats. There was also no change in cyclic nucleotide phosphodiesterase activity in striatal tissue after bromocriptine treatment. Furthermore, incubation of striatal slices in the presence of the phosphodiesterase inhibitor isobutylmethylxanthine did not alter the decreased cAMP response to DA after 2 days of bromocriptine treatment. These results suggest that a decreased number of DA receptor sites may be responsible for the reduced cAMP response to DA in striatal slices after bromocriptine treatment.
Naunyn Schmiedebergs Arch Pharmacol 1978 Sep
PMID:Subsensitivity of the rat striatal dopaminergic system after treatment with bromocriptine: effects on [3H]spiperone binding and dopamine-stimulated cyclic AMP formation. 21 84

Changes in levels of the newly discovered cytidine 3':5'-cyclic monophosphate (cyclic CMP) phosphodiesterase in some representative tissues (cerebral cortex, kidney, intestine, liver, heart, and lung) of guinea pigs from various developmental stages (fetus, neonate, pup, and adult) were studied and compared with those of cyclic AMP and cyclic GMP phosphodiesterases in the same tissues. It was observed that the tissue levels of cyclic CMP phosphodiesterase were invariably the lowest in every one of the fetal tissues examined, the highest in the corresponding tissues from the pups and adult, with intermediate levels seen in some neonatal tissues. The patterns of the ontogenetic changes in levels of cyclic AMP and cyclic GMP phosphodiesterase activities, however, were variable and tissue specific. These findings suggest that the depressed cyclic CMP phosphodiesterase activity (hence, the elevated cyclic CMP concentration) is perhaps a common factor in developing tissues undergoing rapid cell proliferation. The data also suggest that metabolism of cyclic CMP is perhaps more closely related to cell proliferation than the metabolism of cyclic AMP or cyclic GMP.
Proc Natl Acad Sci U S A 1978 Sep
PMID:Depression of cytidine 3':5'-cyclic monophosphate phosphodiesterase activity in developing tissues of guinea pigs. 21 50

Methionine residues have been implicated in the activation of cyclic nucleotide phosphodiesterase by the Ca2+-dependent protein modulator [Walsh, M., & Stevens, F.C. (1977) Biochemistry 16,2742-2749]. Treatment of the modulator with N-chlorosuccinimide in the presence of Ca2+ resulted in selective oxidation of methionine residues at positions 71,72, 76, and, possibly, 109 in the modulator sequence. These residues lie on the surface of the molecule exposed to solvent. This modification has several effects on the modulator protein: (1) the Ca2+-binding properties of the oxidized modulator are changed with apparent loss of high-affinity binding sites, (2) the oxidized protein no longer interacts with phosphodiesterase, and (3) troponin C like activities, viz., Ca2+-dependent change in mobility on urea-polyacrylamide gel electrophoresis and formation of a urea-stable complex with troponin I, are lost upon oxidation of the modulator. The phosphodiesterase binding domain of the modulator protein appears to be located between the second and third Ca2+-binding loops, a region of the molecule known from previous partial proteolysis studies [Walsh, M., Stevens, F.C., Kuznicki, J., & Drabikowski, W.(1977), J. Biol. Chem. 252, 7440-7443] to be exposed in the presence of Ca2+.
Biochemistry 1978 Sep 19
PMID:Chemical modification studies on the Ca2+-dependent protein modulator: the role of methionine residues in the activation of cyclic nucleotide phosphodiesterase. 21 97


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