Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The effect of hypobaric hypoxia on the activities of glutamine synthetase, glutaminase and cyclic 3'5' AMP phosphodiesterase in rat brain was studied after exposure to 25,000' for 6 h. Glutamine synthetase activity was increased in all the regions of brain studied, and addition of gamma amino butyric acid, serotonin and cortisol in vitro produced a differential response. Glutaminase activity decreased in the whole brain. Cyclic 3'5' AMP phosphodiesterase activity decreased in cerebellum, medulla, hypothalamus and pituitary showing an accumulation of cyclic 3'5' AMP in these regions. The results suggest that glutamine synthesis and degradation are regulated in the central nervous system by cyclic AMP and cortisol: Gamma aminoburyric acid and other compounds can modulate the activity of glutamine synthetase and glutaminase.
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PMID:Glutamine synthetase, glutaminase and phosphodiesterase activities in brain under hypoxia: in vitro effect of cortisol, GABA and serotonin on glutamine synthetase. 0 63

1. The effects of secretin and pancreozymin-C-octapeptide and phosphodiesterase inhibitors on the concentration of adenosine 3',5'-cyclic monophosphate (cyclic AMP) and on the release of enzymes from rat pancreas have been studied. 2. In determininging cyclic AMP by means of the saturation assay of Brown et al. ((1971) Biochem. J. 121, 561-563) it is found essential to purify the pancreatic tissue extract by ion-exchange chromatography prior to the assay. 3. Injection of synthetic secretin or pancreozymin-C-octapeptide in anaesthetized rats in a secretory active dose (0.1 nmol) has no effect on the pancreatic cyclic AMP level. 4. Incubation for up to 10 min of pancreatic slices in Krebs-Ringer bicarbonate glucose medium containing 10(-2) M theophylline as phosphodiesterase inhibitor does not result in an increase of the cyclic AMP level. With 10(-2) M 1-methyl-3-isobutylxanthine as phosphodiesterase inhibitor the level is more than doubled after the first min of incubation and remains constant thereafter. 5. Addition of 3-10(-7) M secretin to slices incubated in the presence of 10(-2) M theophylline causes 84% increase of the cyclic AMP level above control, whereas the addition of 3-10(-7) M pancreozymin-C-octapeptide has no significant effect. In the presence of 10(-2) M 1-methyl-3-isobutylxanthine the latter hormone causes significant increases of up to 34% above control during 10 min of incubation. Secretin in this condition augments the cyclic AMP level by up to 296% above control during a 10 min incubation period. Addition of secretin and pancreozymin-C-octapeptide together has no greater effect than of secretin alone. 6. A broken cell fraction of rat pancreas contains adenylate cyclase activity which can be stimulated to 457 and 600% above the basal activity by 3-10(-7) M pancreozymin-C-octapeptide and secretin, respectively. Incubation of pancreatic slices with either hormone has no effect on the cyclic AMP phosphodiesterase activity in the homogenate of these slices. 7. Pancreozymin-C-octapeptide, dibutyryl cyclic AMP, 1-methyl-3-isobutylxanthine and carbamylcholine cause an elevated release of chymotrypsin from pancreatic slices incubated for 2 h in Krebs-Ringer bicarbonate medium, containing 10 mM glucose, while secretin, cyclic AMP and butyric acid have no significant effect. The release of the cytoplasmic enzyme lactate dehydrogenase is also elevated by dibutyryl cyclic AMP, 1-methyl-3-isobutylxanthine and carbamylcholine, but not significantly by pancreozymin-C-octapeptide. 8. The results support the role of cyclic AMP in the action of secretin, and do not exclude a mediating function of this nucleotide in the actions of pancreozymin in rat pancreas.
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PMID:Rat pancreatic adenylate cyclase. IV. Effect of hormones and other agents on cyclic AMP level and enzyme release. 18 33

The inhibitors of cyclic AMP phosphodiesterase (papaverine and 4-(-3-butoxy-4-methoxybenzyl)-2-imidazolidinone), serum-free medium, and x irradiation caused cell death and neurite formation in human neuroblastoma cells in culture (IMR-32), whereas theophylline was ineffective. Prostaglandin (PG) E1, N6O'2-dibutyryl adenosine 3',5'-cyclic monophosphate (dbcAMP) induced neurites without causing cell lethality. Inhibitors of phosphodiesterase and PGE1 increased the intracellular level of cAMP by about 2- and 4-fold respectively, whereas serum-free medium and x irradiation did not. The combination of PGE1 and phosphodiesterase inhibitor was more effective in causing morphological differentiation and in increasing the cAMP level than the individual agent. Sodium butyrate induced cell death and neurites, probably in part by increasing the cAMP level. cAMP, guanosine 3',5'-cyclic monophosphate, and adenosine had no detectable effect on the growth or morphology of neuroblastoma cells in culture. Adenosine 5'-monophosphate produced cell death without causing neurite formation. DbcAMP, and to a much lesser degree, sodium butyrate increased the tyrosine hydroxylase activity.
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PMID:Role of cyclic AMP in differentiation of human neuroblastoma cells in culture. 24 May 3

Some biological and neurochemical properties of the venom of stonefish (Syanceja horrida) were investigated. The venom exhibited oedema-inducing, haemolytic, hyaluronidase, thrombin-like, alkaline phosphomonoesterase, 5' nucleotidase, acetylcholinesterase, phosphodiesterase, arginine esterase, and arginine amidase activities. Recalcification clotting time, prothrombin, and kaolin-cephalin clotting times were increased 1.7-2.3- and 2.4-fold respectively. The LD50 (i.v. mouse) was 300 micrograms/Kg. Its effects on uptake and stimulation of neurotransmitter synthesis and release were observed in rat brain synaptosomes. In the presence of 100 micrograms venom, uptake of [methyl-3H] choline in rat brain synaptosomes was inhibited 70%, while that of 4-amino-n-[U-14C] butyric acid was inhibited 20%. The toxin also stimulated the release of [3H]-acetylcholine from the synaptosomes.
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PMID:Biological activities of Synanceja horrida (stonefish) venom. 136 68

In the accompanying paper it was demonstrated that among several methylxanthine phosphodiesterase inhibitors, only theophylline significantly increased production of the glycoprotein hormone alpha-subunit in HeLa cells, and that this action was synergistic with that of sodium butyrate. A correlation between alpha-subunit induction and cAMP concentrations was not evident. In this report we characterized the effect of these two drugs on the metabolism of alpha-subunit mRNA. Sodium butyrate decreased the apparent half-life of mRNAs encoding alpha-subunit, beta 2-microglobulin, and alpha-tubulin, as well as that of total poly(A)+ RNA and rRNA. Theophylline produced a two- to threefold increase in the apparent half-life of alpha-subunit mRNA but had no effect on the turnover of beta 2-microglobulin, alpha-tubulin, or total poly(A)+ mRNA. An inverse correlation was noted between the apparent half-life of the mRNA and the degree of destabilization elicited by butyrate. It is concluded that alpha-subunit induction by theophylline is in large part due to mRNA stabilization, and that the concerted effect of theophylline and butyrate results from inhibition by theophylline of the butyrate-mediated destabilization of alpha-subunit mRNA combined with the elevation in alpha-subunit gene transcription known to be produced by the fatty acid.
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PMID:Enhancement by theophylline of the butyrate-mediated induction of choriogonadotropin alpha-subunit in HeLa cells. II. Effect of both agents on mRNA turnover. 169 37

Previous studies have shown that disruption of cyclic nucleotide metabolism by phosphodiesterase inhibitors and cyclic nucleotide analogues damages photoreceptors in rod-enriched retinae. In these studies the cone photoreceptors appeared damaged only after the surrounding rods had begun to degenerate. Our aim was to test if cone photoreceptors were susceptible to similar treatments in the absence of rod photoreceptors. We treated pure-cone lizard retinae in an in vitro eyecup preparation. Degeneration of the cones was induced by 10(-3) M, but not 10(-5) M, of the phosphodiesterase inhibitor, isobutylmethylxanthine (IBMX). Changes in the morphology of the cone outer segments were first evident after 10 hr at 24 degrees C. After longer exposures, other retinal cells were also affected. Before morphology was affected, synthesis of proteins of all molecular weights was inhibited throughout the retina. In addition, both retinal cyclic AMP and cyclic GMP levels were elevated, particularly after 2-10 hr. The effects of 10(-3) M IBMX on all of these parameters were still reversible by removal from IBMX after 10 hr. Dibutyryl cyclic AMP at 10(-2) M also inhibited protein synthesis. It also induced degeneration, but less rapidly than 10(-3) M IBMX. Dibutyryl cyclic GMP (10(-2) M) or butyric acid did not significantly affect morphology, or inhibit uptake or incorporation of 3H-leucine by retinae. The concentration of puromycin or cycloheximide that inhibited retinal protein synthesis by the same amount as 10(-3) M IBMX did not affect retinal morphology or cyclic nucleotide levels. One hundred times this concentration induced pyknosis in the nuclear layers of the retina before disturbing cone outer segment organization. In conclusion, millimolar IBMX and dibutyryl cyclic AMP damage cones even without neighboring rods, indicating that elevated cyclic nucleotide levels are toxic to cones per se. Retinal protein synthesis is also inhibited by damaging levels of cyclic nucleotides, but it does not seem to be responsible for the deterioration of cone structure.
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PMID:Photoreceptor degeneration in a pure-cone retina. Effects of cyclic nucleotides, and inhibitors of phosphodiesterase and protein synthesis. 243 72

The role of cyclic AMP in regulating the production of angiotensin converting enzyme (ACE) was investigated using cultured bovine aortic endothelial cells. Addition of dibutyryl cAMP [Bu)2cAMP) at 100 microM increased the ACE activity to 126% of control (P less than 0.005). This effect was blocked by either actinomycin D (0.1 microgram/ml) or cycloheximide (1.7 microM) indicating that RNA as well as protein synthesis was required for induction of the enzyme. After addition of (Bu)2cAMP, a lag period of 8 h was observed before increased ACE activity was detected. The stable analogues, 8-bromo cAMP (100 microM) and N6-monobutyryl cAMP (100 microM) also increased ACE activity but cAMP (100 microM) and O2-monobutyryl cAMP (100 microM) had no effect, in keeping with their susceptibility to phosphodiesterase in this system. Sodium butyrate (100 microM) was also inactive. The effect of (Bu)2cAMP on ACE was still observed in the presence of a maximal dose of dexamethasone, indicating that (Bu)2cAMP stimulates by mechanism(s) independent of the previously observed action of glucocorticoids on these cells. The phosphodiesterase inhibitor IBMX caused a dose-related increase in ACE activity with a threshold at 30 microM (P less than 0.05) and produced a 4-fold increase above control at 1 mM IBMX.
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PMID:Angiotensin converting enzyme induction by cyclic AMP and analogues in cultured endothelial cells. 244 4

The effect of caffeine on the transport, metabolism and ultrastructure of the colon were determined. Segments of proximal colon were excised from the anesthetized rat and prepared for radioisotopic tracing of ion transport in the flux chambers or oxidative metabolism in an incubator. Other segments were fixed before or after caffeine administration for electron microscopy. The isolated rat colon actively transported both Na+ and Cl- in the absorptive direction, mucosa to serosa. Serosal addition of 10 mmol/l caffeine abolished the smaller Na+ transport but did not significantly affect the larger Cl- transport. The electrical potential difference and the short-circuit current rose accordingly. Although the oxidation of glucose was inhibited by 35%, caffeine had no significant effect on the oxidation of the fatty acid, butyric acid. Comparable metabolic responses were obtained using the isolated terminal ileum of the rat. Neither the height nor the density of the microvilli in the proximal colon were affected significantly by caffeine. It may be concluded that caffeine, unlike theophylline, effectively preserves the normal absorptive condition of the colon. Thus, caffeine may have actions other than inhibition of phosphodiesterase in the distal intestine.
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PMID:Effects of caffeine on transport, metabolism and ultrastructure of isolated rat colon. 299 97

The effect of different phosphodiesterase (PDE) inhibitors on the antigen or 48/80 induced histamine release from isolated Hooded Lister rat mast cells was tested. The unselective PDE inhibitors theophylline (2.5 mM) and IBMX (0.2 mM) and the selective cyclic GMP PDE inhibitor M & B 22948 (0.1 mM) inhibited the antigen induced histamine release by 50% while 48/80 induced release was inhibited by about 25%. The cyclic AMP selective PDE inhibitors ICI 63197 (0.5 mM) or Ro 20-1724 (0.2 mM) had no effect on 48/80 induced histamine release but tended to enhance antigen induced release. There was no correlation between the measured levels of cyclic AMP and the effect on histamine release by the investigated PDE inhibitors. Cyclic AMP or cyclic GMP up to 10(-3) M did not affect the anaphylactic histamine release. Dibutyryl-cAMP and dibutyryl-cGMP (10(-4) M) both inhibited the release about 20% but this effect could be explained by the effect of butyric acid as sodium butyrate (2 X 10(-4) M) also inhibited the release by 20%. The presence results suggest that cyclic nucleotides are not important regulators of histamine release from isolated mast cells.
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PMID:Evidence against a role of cyclic nucleotides in the regulation of anaphylactic histamine release in isolated rat mast cells. 616 52

Recently the cDNA for two different forms of TNF receptor, with gene products of molecular masses of 60 and 80 kDa, have been cloned. In the present report, we investigated the effects of phorbol ester and dibutyryl cAMP on the regulation of the transcript for each type of TNF receptor in U-937 cells. Our results indicate that exposure of these cells to either phorbol ester or dibutyryl cAMP increases the steady state mRNA levels of the 80 kDa form. This effect is dose- and time-dependent. The induction of the p80 receptor transcript by PMA and dibutyryl cAMP was additive suggesting independent mechanisms of induction. Under identical conditions, both agents failed to induce the transcript for the p60 form of the TNF receptor. As demonstrated by actinomycin D pulse-chase experiment, the mRNA for the p80 receptor was found to be highly stable with an approximate half-life of 16 h. No significant change in the half-life was observed when cells were treated with phorbol ester. The mechanisms by which phorbol ester and dibutyryl cAMP induce the upregulation of p80 receptor mRNA appear to be different. Induction of receptor transcript by cycloheximide suggests the presence of a labile repressor protein. Interestingly, the effect of cycloheximide on the induction of the p80 mRNA was found to be additive with that of dibutyryl cAMP but not with phorbol ester. 1-(5-Isoquinolinylsufonyl)-2-methylpiperazine (H7) and N[2-(methylamino) ethyl]-5-isoquinolinesulfonamide (H-8), inhibitors of protein kinase C and protein kinase A, respectively, both inhibited the phorbol ester-mediated induction of the p80-transcript but not that mediated through dibutyryl cAMP. Since dibutyryl cAMP undergoes intracellular dissociation into cAMP and butyric acid, we found that exposure of cells to sodium butyrate alone could induce p80 mRNA in a dose-dependent manner, thus suggesting the role of histone hyperacetylation. Furthermore forskolin treatment, an intracellular inducer of cAMP, increased the receptor transcript level whereas isobutylmethylxanthine, an inhibitor of phosphodiesterase, had no effect. Interestingly, while the p80 form of the TNF receptor mRNA levels was elevated by both phorbol ester and dibutyryl cAMP, only dibutyryl cAMP increased the TNF binding; phorbol ester treatment decreased the binding activity. Thus, our results demonstrate that the genes for the two forms of TNF receptors are differentially regulated. Furthermore, the mechanism of regulation by PMA differs from that by dibutyryl cAMP.
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PMID:Regulation of two forms of the TNF receptors by phorbol ester and dibutyryl cyclic adenosine 3',5'-monophosphate in human histiocytic lymphoma cell line U-937. 768 79


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