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

---

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

Ethanol and other alcohols stimulate adenylate cyclase activity in various tissues and potentiate its stimulation by some hormones. This effect, however, usually requires a high alcohol concentration. In some cases, an unknown substance, different from cyclic AMP, was formed from ATP in the presence of an alcohol and mimicked stimulation of adenylate cyclase. Ethanol inhibits phosphodiesterase activity in some tissues. In the brain, only the low affinity enzyme of pons-medulla region is inhibited. ATP levels and ATPase activities are affected by ethanol treatment and this can lead to secondary changes of the cyclic AMP levels. Cyclic AMP levels in the brain and liver are decreased by acute ethanol administration while levels in other organs are unchanged. High doses of ethanol inhibit the postdecapitation-induced rise of cyclic AMP level in the brain while low ethanol doses potentiate the postdecapitation rise of cyclic AMP in the lower brain stem. Chronic ethanol administration increases basal adenylate cyclase activity and cyclic AMP levels, and decreases stimulation of adenylate cyclase by norepinephrine in the brain. In contrast, the stimulation of cyclic AMP formation by norepinephrine and other biogenic amines is increased in the brain of ethanol-withdrawn animals. Chronic administration of ethanol affects also cyclic AMP levels and cyclic AMP formation in some peripheral organs. Cyclic AMP might be involved in ethanol-induced fatty liver, since it activates hepatic lipase and might also participate in the fatty acid oxidation.
...
PMID:Interactions of ethanol with cyclic AMP. 16 56

The effects of ethanol on adenylate cyclase and phosphodiesterase activity in vitro, and on cyclic AMP, ATP and adenosine levels in vivo were studied. Ethanol appeared to affect the cyclic AMP system indirectly, probably through its effect on neurotransmitter release or on adenosine formation.
...
PMID:Effect of ethanol on the cyclic AMP system in rat brain. 18 35

In this study ethanol and certain other short-chain aryl (benzyl and phenethyl) and aliphatic (methyl, propyl, butyl, and amyl) alcohols produced up to 10-fold increases in cyclic AMP (cAMP) concentrations in purified human peripheral blood lymphocytes. Ethanol concentrations as low as 80 mg/dl produced significant elevations in lymphocyte cAMP. Significant but less marked augmentation of cAMP in response to alcohols was observed in human platelets, human granulocytes, and rabbit alveolar macrophages. The mechanism of the alcohol-induced cAMP accumulation is probably secondary to membrane perturbation and consequent activation of adenylate cyclase, because ethanol directly stimulated this enzyme in lymphocyte membrane preparations but had no effect on lymphocyte phosphodiesterase activity. Lysosomal enzyme release, by phagocytosing human leukocytes, and aminoisobutyric acid transport in mitogen-stimulated human lymphocytes were shown to be inhibited by ethanol and other alcohols at concentrations which also elevate cAMP. In general, the magnitude of the inhibition of these inflammatory processes correlated with the ability of the alcohol to elevate cAMP concentrations. Lectin-and anti-thymocyte globulin-induced lymphocyte mitogenesis was inhibited or unaffected depending upon both the concentration and type of mitogenic stimulus and the concentration and type of alcohol utilized. Inflammatory mediator release from rat mast cells also was inhibited by ethanol and certain other alcohols, but whole cell cAMP was not increased. Ethanol may alter these inflammatory responses and other biologic processes at least in part by modulating cellular levels of cAMP.
...
PMID:Stimulation by alcohols of cyclic AMP metabolism in human leukocytes. Possible role of cyclic AMP in the anti-inflammatory effects of ethanol. 19 24

Ethanol activates phosphoinositide-specific phospholipase C in human platelets resulting in the mobilization of intracellular calcium and shape change (Arch. Biochem. Biophys. 260, 480-492, 1988). Preincubation of platelets with agents that increase levels of cAMP (i.e., forskolin, prostacyclin) inhibited these responses to ethanol in a concentration- and time-dependent manner. The inhibitory effect was potentiated by the phosphodiesterase inhibitor, isomethybutylxanthine. When added after ethanol, these agents also reversed platelet shape change and lowered cytosolic free calcium to basal levels. The results demonstrate a direct inhibitory effect of cAMP on the ethanol-induced activation of phospholipase C.
...
PMID:Inhibition of ethanol-induced platelet activation by agents that elevate cAMP. 216 73

We have conducted studies to obtain practical knowledge regarding the stability, digestion, and analytical determination of the content of 8-hydroxy-2-deoxy-guanosine (8-OHdG) in oxidatively damaged DNA. Utilizing H2O2 plus uv light to form oxidatively damaged DNA, we found that storage of the DNA at -20 degrees C at alkaline pH caused a significant loss of 8-OHdG, whereas storage at -20 degrees C at neutral or acidic pH prevented loss of 8-OHdG. The 8-OHdG within DNA is stable at 100 degrees C for at least 15 min. Formation of 8-OHdG within DNA using uv light and H2O2 as a hydroxyl free radical-generating system yields the highest amounts when low levels of phosphate buffer are used; but the use of Tris or citrate buffers causes a lower yield of 8-OHdG because these buffers act as scavengers for the hydroxyl free radicals. Independent assessment of hydroxyl free radical flux by the use of salicylate trapping allows assessment of competitive radical reactions. Ethanol washing of plastic microfuge tubes prior to DNA enzymatic digestion improved the yield of 8-OHdG and reduced the variability between samples. Digestion of the oxidatively damaged DNA by the use of a method involving DNase I, endonuclease, phosphodiesterase, and alkaline phosphatase produced the highest yield of 8-OHdG.
...
PMID:Conditions influencing yield and analysis of 8-hydroxy-2'-deoxyguanosine in oxidatively damaged DNA. 222 56

Ethanol causes mycelial growth of Candida tropicalis Pk 233, which is associated with enhanced metabolism of phosphatidylinositol at the mid-log phase of growth, and the effects of ethanol are prevented by concomitant addition of myo-inositol (FEBS Lett. 214, 127-129, 1987). Ethanol induced also a marked increase in cellular content of cAMP at the mid-log phase, and myo-inositol abolished this effect of ethanol. The elevated level of cAMP content caused by ethanol was gradually lowered through the late-log and stationary phases and reached to control level. Very similar effects of ethanol and myo-inositol were observed in adenylate cyclase activity, while the activity of cAMP phosphodiesterase was not affected by ethanol. The ethanol-induced change in cAMP content was therefore ascribed to that in adenylate cyclase activity. These results suggested that cAMP plays an important role in combination with phosphatidylinositol turnover in the development of mycelial form in this dimorphic yeast.
...
PMID:Increase in cyclic AMP content with enhanced phosphatidylinositol turnover in the cells of Candida tropicalis during mycelial growth caused by ethanol. 254 37

The effects of ethanol on parathyroid hormone (PTH)-induced increases in adenosine 3':5'-phosphate (cAMP) concentrations were studied in renal cortical tubules of hamsters in vitro. Ethanol concentrations between 0.1 and 3% were found to augment the PTH response in a dose-related way while, concentrations greater than 3% produced a dose-related inhibition of the PTH response. In the absence of PTH, ethanol did not significantly elevate cAMP accumulations at any concentrations tested. In contrast to its effect on intact tubule cells, ethanol did not alter either adenylate cyclase or phosphodiesterase in renal cortical homogenates. Indomethacin, however, produced a concentration-related inhibition of the ethanol-potentiated response without altering the effects of PTH alone. The results suggest a possible involvement of prostaglandins in the potentiating effect of ethanol on the PTH-dependent accumulation of cAMP in renal tubules.
...
PMID:Enhancement by ethanol of parathyroid-hormone-stimulated cyclic AMP accumulation in isolated renal tubules. 630 64

The authors tested the hypothesis that ethanol or its metabolite acetaldehyde might interfere in cyclic guanosine monophosphate (GMP) metabolism in coronary smooth muscle cells. Ethanol at the physiologically relevant concentration of 4.0 mg/mL or more significantly decreased basal guanylate cyclase activity and inhibited activation of the enzyme by sodium nitroprusside (SNP) in cultured porcine coronary smooth muscle cells. Two isoforms of phosphodiesterase (PDE), cyclic GMP-specific form and calmodulin-stimulated form, were both inhibited by 12.0 mg/mL or more ethanol. Intact cell study revealed that although 12.0 mg/mL or more ethanol was needed to significantly decrease cyclic GMP accumulation in control cells, 4.0 mg/mL or more ethanol significantly inhibited the increase of cyclic GMP accumulation induced by 1 microns SNP. Acetaldehyde showed similar effects, but the concentrations involved were more than physiological. Thus, ethanol may decrease cellular cyclic GMP levels and attenuate cyclic GMP accumulation in response to SNP in coronary smooth muscle cells by inhibiting soluble guanylate cyclase activity at physiologically relevant concentrations.
...
PMID:Ethanol modulates cyclic GMP metabolism in cultured coronary smooth muscle cells. 809 30

The time course of the effects of ethanol withdrawal on brown and white adipose tissue hormone-sensitive lipase, cAMP production, and phosphodiesterase have been investigated after chronic drinking or liquid diet schedules. Chronic drinking significantly reduced brown adipose tissue hormone-sensitive lipase activity and cAMP levels from control. During withdrawal, there was a rebound increase to 200% control, peaking 9 h into withdrawal. White adipose tissue hormone-sensitive lipase activity and cAMP accumulation were significantly raised by both treatment schedules. Ethanol liquid diet produced a significant fall in adipose tissue hormone-sensitive lipase activity and cAMP accumulation. In brown fat, there was a rebound increase in hormone-sensitive lipase activity and cAMP; in white fat, no rebound was observed. In brown fat, the reductions in hormone-sensitive lipase activity and cAMP accumulation after chronic drinking coincided with an increase in phosphodiesterase activity. In white fat, the rise in cAMP and hormone-sensitive lipase activation coincided with a decrease in phosphodiesterase activity. We conclude that the effects of chronic ethanol on hormone-sensitive lipase activity are cAMP-dependent and mediated via alterations in phosphodiesterase activity.
...
PMID:Changes in adipose tissue hormone-sensitive lipase activity and cAMP during ethanol withdrawal. 1110 16

Ethanol exposure in airway epithelium increases cyclic AMP (cAMP)-dependent protein kinase (PKA) activity. Activation of PKA and cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) has been shown to increase ciliary beat frequency (CBF) in bovine bronchial epithelial cells (BBECs). We have shown that biologically relevant concentrations of ethanol stimulate increases in CBF in a nitric oxide-dependent manner, mediated through elevated cAMP levels and subsequent PKA activation. This ethanol-driven rapid and transient increase in CBF occurs 15 to 30 min after exposure to 100 mM ethanol. However, after prolonged exposure to 100 mM ethanol (>/=6 h), CBF and the catalytic activity of PKA return to baseline levels. We hypothesize that cyclic nucleotide-dependent phosphodiesterase (PDE) activity attenuates the duration of ethanol-stimulated ciliary motility. The effect of ethanol on the PDE activity in BBECs was determined through direct assay of catalytic activity. When BBECs were incubated with 100 mM ethanol, significant increases in cAMP levels occurred within 1 h, with corresponding increases in PKA activity. Treatment of BBECs with 100 mM ethanol increased cAMP-PDE activity significantly by 4 h. 3-Isobutyl-1-methylxanthine, Ro 20-1724, and rolipram inhibited ethanol-stimulated cAMP-PDE activity. These agents inhibited ethanol-stimulated cAMP-PDE activity and increased the magnitude of ethanol-stimulated PKA activity observed under the same conditions. These findings support the idea that acute exposure (<6 h) to ethanol increases cAMP levels, and the associated increase in PKA activation is regulated by cAMP-dependent PDE, specifically PDE4. Other compensatory mechanisms however, may be responsible for the down-regulation of PKA, which occurs after chronic epithelial exposure (>/=6 h) to ethanol.
...
PMID:Ethanol increases phosphodiesterase 4 activity in bovine bronchial epithelial cells. 1461 9


1 2 Next >>

---