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)

Cyclic AMP and folic acid act as chemotactic factors in Dictyostelium discoideum. Both agents, when applied extracellularly, also control cell development from the growth stage to the acquisition of aggregation competence. Cyclic AMP phosphodiesterase and folate deaminase are extracellular enzymes whose activity is regulated during early differentiation of D. discoideum cells. The two enzymes help control the extracellular levels of cyclic AMP and folic acid. The substrates cyclic AMP and folic acid each increase the extracellular activity of folate deaminase as well as phosphodiesterase. The specificity of extracellular phosphodiesterase regulation by cyclic AMP indicates that the effect is mediated by specific cyclic AMP receptors rather than the catalytic site of cell surface phosphodiesterase. To some extent cyclic AMP and folic acid are interchangeable with respect to regulating differentiation and enhancing enzymatic inactivation of intercellular signals. Thus the two extracellular signals may share a common cellular pathway of signal transduction. The regulation of folate deaminase and phosphodiesterase by folic acid does not always parallel the folic acid effects on development. Pulses of folic acid stimulate development of aggregation competence, whereas a continuous flux inhibits. In contrast, either continuous flux or pulses of folic acid increase the deaminase and phosphodiesterase activities.
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PMID:Folate deaminase and cyclic AMP phosphodiesterase in Dictyostelium discoideum: their regulation by extracellular cyclic AMP and folic acid. 626 63

The activities of cyclic AMP regulatory enzymes (adenylate cyclase and phosphodiesterase) were studied in rat gastrocnemius muscle after denervation. Basal adenylate cyclase activity in whole homogenate increased progressively from the 3rd day reaching values more than 7-fold those of the controls 30 days after denervation. No significant differences between the contralateral and denervated muscle were detected as regards adenylate cyclase activation by catecholamines or NaF. Carbamylcholine was with effect. Cyclic AMP phosphodiesterase activity increased significantly at 3 days after denervation as was still significantly elevated at 60 days.
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PMID:Effect of denervation on cyclic amp regulating enzymes in the rat gastrocnemius muscle. 626 4

Changes in the activity of cyclic AMP phosphodiesterase during differentiation of rabbit bone marrow erythroid cells were investigated. The cells were separated by velocity sedimentation at unit gravity into six fractions corresponding to different stages of development: proerythroblasts, basophilic cells, polychromatic cells, early orthochromatic and late orthochromatic cells and reticulocytes. Cyclic AMP phosphodiesterase was found to be very active in the most immature cells, the proerythroblasts, which also have the highest content of cyclic AMP. After differentiation into basophilic erythroblasts, a 4-fold decrease in cyclic AMP phosphodiesterase activity was observed. In these cells the amount of cyclic AMP was about 80% lower than that in proerythroblasts. In polychromatic cells a further drop in phosphodiesterase activity occurred. After the final cell division the enzyme activity was very low and the levels of cyclic AMP in the early and late orthochromatic cells remained constant. Kinetic studies demonstrated a heterogeneity of erythroid cell cyclic AMP phosphodiesterase: high affinity, low-Km (5.5 X 10(-6) M) and low affinity, high-Km (0.1 X 10(-3) M) enzymes were found. The phosphodiesterase activity was dependent on the presence of Mg2+ and was activated by Ca2+ at low Mg2+ concentrations (1 mM). The changes in cyclic AMP phosphodiesterase activity during differentiation and maturation of erythroid cells suggest the possible importance of this enzyme in the physiological control of cyclic AMP concentrations in developing erythroblasts. The loss of cyclic AMP phosphodiesterase activity after cessation of cell division supports the concept of the significance of the final cell division in erythroblast differentiation.
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PMID:Cyclic AMP phosphodiesterase activity during differentiation of rabbit erythroid bone marrow cells. 627 22

Responsiveness to catecholamines was studied in two different strains of rat glioma C6 cells. The C6 cells of low passage possessed a high capacity to accumulate cyclic AMP in response to (-)-isoproterenol. Cholera toxin was also able to stimulate cyclic AMP accumulation in these cells. High passage C6 cells were unresponsive to (-)-isoproterenol or to cholera toxin except in the presence of a high concentration of phosphodiesterase inhibitor. The affinity of beta-adrenergic receptors on both strains for (-) [3H] dihydroalprenolol was similar; however, C6 low passage possessed several times the number of beta-adrenergic receptors found in C6 high passage. This difference correlated with the difference found in (-)-isoproterenol-stimulated adenylate cyclase between C6 low passage and high passage. The sodium fluoride-stimulated adenylate cyclase was similar in both strains. Cyclic AMP phosphodiesterase activity was 2-3 times higher in homogenates of C6 high passage than in low passage. In intact cells, the rate of breakdown of cyclic AMP was 5-times faster in C6 high passage than in low passage. Thus, differences in beta-adrenergic receptor number and phosphodiesterase activity explain in part the lack of responsiveness of C6 high passage. Our studies indicate that continuous subculturing of rat glioma C6 cells led to complex alterations in the beta-adrenergic receptor-adenylate cyclase system.
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PMID:Differences in the beta-adrenergic responsiveness between high and low passage rat glioma C6 cells. 627 15

Cyclic AMP phosphodiesterase (PDE) activity reaches a peak during the aggregation stage of development where it functions to regulate extracellular levels of cAMP. During the subsequent differentiation of the two cell types at the culmination stage, the activity reappears but only in stalk cells. We found that extracts from the culmination stage contained PDE which could be activated by preincubation with Mg2+ and dithiothreitol (DTT), a treatment which is known to release an endogenous inhibitor from the aggregation stage enzyme. When the culmination stage extracts were subjected to chromatography on Biogel P300, two peaks of activity were eluted, PDE-I (Mr greater than 260,000) and PDE-II (Mr 100,000). Treatment of the fractions with Mg-DTT did not affect the low-molecular-weight enzyme but caused activation of the high-molecular-weight enzyme and the appearance of a third, intermediate form. Kinetic analysis of the two peaks revealed Km values for cAMP of 2 mM and 10 microM for PDE-I and PDE-II, respectively. We tested the possibility that these forms of the enzyme might be distributed differently in the two cell types by measuring the Km for cAMP and the effect of Mg-DTT treatment on isolated sections of stalk and spore cells. The spore sections contained a high Km form of the enzyme (0.3 mM) which was activated by preincubation with Mg . DTT whereas stalk sections contained a low Km form (3 microM) which was not affected by the activation treatment. We conclude that both cell types contain enzyme protein and that the apparent localization of PDE activity in stalk cells is due to the inhibition of activity in spore cells.
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PMID:Cell type specific inhibition of cAMP phosphodiesterase activity during terminal differential in Dictyostelium discoideum. 629 19

Changes in the cellular content of cyclic AMP and in the activities of adenylyl cyclase, cyclic AMP phosphodiesterase and cyclic AMP-dependent protein kinases during differentiation of rabbit bone marrow erythroid cells were investigated. The cells were separated by velocity sedimentation at unit gravity into six fractions corresponding to different stages of development: proerythroblasts, basophilic erythroblasts, polychromatic cells, early orthochromatic and late orthochromatic cells and reticulocytes. Adenylyl cyclase activity was found to decrease continuously as the cells developed, from approx. 180 pmoles cyclic AMP formed/mg of protein/20 min in proerythroblasts to 10 pmoles in circulating reticulocytes. The proerythroblasts were the richest cells in cyclic AMP which is present at a cellular concentration of approx. 1.4 microM. In basophilic cells the cyclic AMP content was about 80% lower than in proerythroblasts. No further changes in cyclic AMP levels were observed after the final cell division. Cyclic AMP phosphodiesterase was found to be very active in the most immature cells, the proerythroblasts. After differentiation into basophilic erythroblasts, a 4-fold decrease in cyclic AMP phosphodiesterase activity occurred. In polychromatic cells there was a further drop in phosphodiesterase activity and after the last cell division the enzyme activity was constant and very low. Both cytosolic cyclic AMP-binding capacity and cytosolic cyclic AMP-dependent protein kinase activity decreased in dividing rabbit bone marrow erythroblasts when calculated in terms of cell number but remained constant per cell volume. After the final cell division, cyclic AMP-dependent protein kinase activity did not change further, whereas cyclic AMP-binding capacity declined. There were no qualitative but only quantitative changes in the cyclic AMP-binding proteins that are present in the cytosol of developing erythroblasts. In the immature cells, the apparent Kd for the interaction of binding proteins with cyclic AMP was 4 . 10(-8) M. The data suggest that changes in cyclic AMP-binding activity during differentiation of erythroid cells are due both to changes in the amount of binding proteins and their affinity for cyclic AMP. The phosphorylation of rabbit erythroblast plasma membrane proteins by membrane-associated protein kinase(s) was found to be cyclic AMP-dependent in dividing cells during the early stages of differentiation. When the erythroid cells reach the non-dividing stage in their development, autophosphorylation of membrane ghosts was no longer stimulated by cyclic AMP.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Characteristics of the adenylyl cyclase system of differentiating rabbit bone marrow erythroblasts. 632 45

Cyclic nucleotide metabolism was examined in the retina and in the retinal pigment epithelium (RPE)-choroid complex of the rds mouse (020/A), a mutant in which discrete photoreceptor outer segment disc structures fail to develop. In retinas of both rds and control (Balb/c) mice, cyclic AMP levels peak at 10-15 days (20-25 pmol mg-1 protein). The level drops to about 10 pmol mg-1 at about one month in normal retinas but remains high in affected retinas. Cyclic GMP levels increase five-fold in Balb/c retinas as ROS develop whereas, in affected retinas, the levels remain constant and low (about 5 pmol mg-1). In RPE-choroid, cyclic nucleotide levels are similar in control and affected mice. Cyclic AMP phosphodiesterase (PDE) activity is somewhat higher in affected than in control retinas; conversely, cyclic GMP-PDE is lower. Both cyclic AMP-PDE and cyclic GMP-PDE activities are different in normal and affected RPE-choroid. Thus, although the rds (020/A) mouse belongs to the early-onset photoreceptor dysplasia group of hereditary retinal degenerations on a morphological basis, it does not exhibit high retinal cyclic GMP levels and thus appears to be distinct from other animals exhibiting early postnatal photoreceptor dysfunction.
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PMID:Cyclic nucleotide content and phosphodiesterase activity in the rds mouse (020/A) retina. 632 41

Cyclic AMP phosphodiesterase (PDE) isozymes were isolated and characterized from the soluble fraction of rat parotid gland. Four main peaks containing PDE activity were obtained by Q-Sepharose Fast Flow column chromatography. The four peaks were identified as PDEs I-IV by kinetic properties, molecular-weight analysis and their responses to effectors and inhibitors.
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PMID:Characterization of cyclic AMP phosphodiesterase isozymes in rat parotid gland. 779 30

Cyclic AMP phosphodiesterase (PDE) type 4 has been the subject of considerable interest as a potential molecular target for treating cutaneous inflammatory and allergic disorders; however, little is known regarding the expression of PDE 4 isogenes in human keratinocytes, the predominant cell type present in the epidermis. In this study, we investigated the expression of PDE 4 subtypes in epidermal cells (primary keratinocytes derived from breast skin, epidermoid cell lines A431, KB, and HaCaT) using reverse transcriptase polymerase chain reaction. Analysis of the amplified cDNA showed that there were differences in the expression of PDE 4 isogenes in the epidermal cells. Constitutive expression of the PDE 4 isozymes was detected in untreated epidermal cells at different levels. Transcripts for PDE 4B and 4D were abundantly expressed in breast skin-derived keratinocytes, whereas transcripts for PDE 4A, 4C, and 4D were present in HaCaT cells and transcripts for all the PDE 4 isotypes were present in A431 and KB. PDE 4A and 4C were detectable in HaCaT cells in equal amounts, but PDE 4C was only marginally expressed in the other cells. Of the four isogenes, PDE 4D was abundantly expressed in all the cells. Elevation of intracellular levels of cAMP by forskolin increased the expression of all the hPDE 4 isogenes 2-3-fold as revealed by semiquantitative reverse transcriptase polymerase chain reaction. Western blot analysis of extracts from control and forskolin or dibutyryl cAMP-treated A431 and KB cells demonstrated the presence of proteins with a molecular mass identical to that corresponding to recombinant human PDE 4B. Together, these findings show that PDE 4 isogenes are expressed in keratinocytes to a different degree and that their expression can be modulated by intracellular levels of cAMP.
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PMID:Cyclic nucleotide phosphodiesterase 4 subtypes are differentially expressed by primary keratinocytes and human epidermoid cell lines. 950 51


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