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)

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.
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PMID:Multiple cyclic nucleotide phosphodiesterases in rat kidney. 0 May 37

Guanylate cyclase and cyclic-GMP phosphodiesterase activities were measured in homogenates of mammary glands from virgin, pregnant, and lactating mice. Guanylate cyclase activities increased 35% in mammary tissues during pregnancy, and a further 40% increase was observed during lactation. Cyclic-GMP phosphodiesterase activity also increased during pregnancy but activities were not different in glands from lactating mice vs glands from pregnant mice. These results are discussed with regard to a possible role of cyclic-GMP in regulating lactational processes.
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PMID:Guanylate cyclase and cyclic-GMP phosphodiesterase activities in mammary glands of mice during pregnancy and lactation. 0 96

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.
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PMID:Cyclic nucleotides and platelet aggregation. Effect of aggregating agents on the activity of cyclic nucleotide-metabolizing enzymes. 0 49

An increase in mouse cerebellar C-GMP levels during acute morphine treatment was observed, which was possibly related to the decrease in C-GMP phosphodiesterase levels also observed in acute treatment. Chronic treatment lowered C-GMP levels as did abrupt withdrawal without naloxone.
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PMID:Effects of morphine administration on cerebellar guanosine 3',5'-monophosphate. 1 Nov 21

Phosphodiesterase activities of horse (and dog) thyroid soluble fraction were compared with either cyclic AMP (adenosine 3':3'-monophosphate) or cyclic GMP (guanosine 3':5'-monophosphate) as substrate. Optimal activity for cyclic AMP hydrolysis was observed at pH 8, and at pH 7.6 for cyclic GMP. Increasing concentrations of ethyleneglycol bis(2-aminoethyl)-N,N'-tetraacetic acid inhibited both phosphodiesterase activities; in the presence of exogenous Ca2+, this effect was shifted to higher concentrations of the chelator. In a dialysed supernatant preparation, Ca2+ had no significant stimulatory effect, but both Mg2+ and Mn2+ increased cyclic nucleotides breakdown. Mn2+ promoted the hydrolysis of cyclic AMP more effectively than that of cyclic GMP. For both substrates, substrate velocity curves exhibited a two-slope pattern in a Hofstee plot. Cyclic GMP stimulated cyclic AMP hydrolysis, both nucleotides being at micromolar concentrations. Conversely, at no concentration had cyclic AMP any stimulatory effect on cyclic GMP hydrolysis. 1-Methyl-3-isobutylxanthine and theophylline blocked the activation by cyclic GMP of cyclic GMP of cyclic AMP hydrolysis, whereas Ro 20-1724 (4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone), a non-methylxanthine inhibitor of phosphodiesterases, did not alter this effect. In dog thyroid slices, carbamoylcholine, which promotes an accumulation of cyclic GMP, inhibits the thyrotropin-induced increase in cyclic AMP. This inhibitory effect of carbamoylcholine was blocked by theophylline and 1-methyl-3-isobutylxanthine, but not by Ro 20-1724. It is suggested that the cholinergic inhibitory effect on cyclic AMP accumulation is mediated by cyclic GMP, through a direct activation of phosphodiesterase activity.
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PMID:Cyclic nucleotide hydrolysis in the thyroid gland. General properties and key role in the interrelations between concentrations of adenosine 3':5'-monophosphate and guanosine 3':5'-monophosphate. 1 74

1. Dibutyryl cyclic AMP (Db cAMP, 75-500 microgram/kg), injected into the lateral ventricle of the brain of the cat increased blood pressure, heart rate and splanchnic discharge rate. 2. ATP, but not AMP, induced similar changes; GMP in small doses increased blood pressure. 3. A number of drugs are known to activate adenylate cyclase-induced hypertension, tachycardia and increase splanchnic discharge rate. This was shown for TRH, tetracosactide and a new beta2-adrenoceptor stimulant, NAB 365. 4. Injection into the lateral ventricle of theophylline or Ro 7/2956, both inhibitors of phosphodiesterase, similarly increased blood pressure. 5. Histamine administered by the same route induced similar reactions; it is not known if this action was exerted by activation of H1- or H2-receptors. 6. Somatostatin, known to reduce cAMP levels, induced a small but significant decrease in blood pressure. Melanocyte stimulating hormone release inhibiting factor (MIF) and TSH were ineffective. 7. These results provide evidence for the possibility of a role for cAMP in the central regulation of blood pressure at suprabulbar levels.
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PMID:Cyclic 3'5'-adenosine monophosphate and central circulatory control in cats and dogs. 2 Feb 56

It is unclear what factors control the secretion of pulmonary surface active material from alveolar type II cells in vivo. Other workers have suggested that cholinergic stimuli, adrenergic stimuli, and prostaglandins may all stimulate secretion. We isolated type II cells from the lungs of rats by treatment with elastase, discontinuous density centrifugation, and adherence in primary culture. beta-Adrenergic agonists, but not cholinergic agonists, caused an increase in the release of [(14)C]disaturated phosphatidylcholine, the major component of surface-active material, from type II cells in culture. The beta-adrenergic effect was stereo-selective, (-)-isoproterenol being 50 times more potent than (+)-isoproterenol. Terbutaline, 10 muM, a noncatecholamine beta-2 adrenergic agonist, caused a release of 2.0+/-0.5 (mean+/-SD) times the basal release of [(14)C]disaturated phosphatidylcholine in 3 h; the concentration of terbutaline causing half maximal stimulation was 800 nM. The terbutaline effect was blocked by propranolol, a beta-adrenergic antagonist (calculated K(d) = 6 nM), but not by phentolamine, an alpha-adrenergic antagonist. Isobutylmethylxanthine, a phosphodiesterase inhibitor, and 8-Br cyclic AMP, but not 8-Br cyclic guanosine monophosphate, also stimulated release. We conclude that type II cells secrete disaturated phosphatidylcholine in response to treatment with adrenergic stimulation.
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PMID:Pulmonary alveolar type II cells isolated from rats. Release of phosphatidylcholine in response to beta-adrenergic stimulation. 3 31

1. The ouabain-insensitive Na efflux in barnacle muscle fibres is promptly stimulated by injection of cyclic GMP. The minimal effective injected concentration is found to be about 10(-7) M. This effect of cyclic GMP could not be mimicked by injecting 5'-GMP. 2. External application of ouabain (10(-4) M) to fibres not pretreated with ouabain during the stimulatory response to cyclic GMP causes some inhibition of the Na efflux indicating that cyclic GMP does not cause appreciable inhibition of the Na:K pump. 3. The magnitude of the stimulatory response to injected cyclic GMP depends on the external Ca2+ concentration, as well as pHe but not on the Na+, K+ or Mg2+ concentration. It also depends on pHi, since acidification of HCO3-containing ASW leads to a greater enhancement of the response to cyclic GMP than is observed with acidified HERPES-ASW. 4. Stabilization of myoplasmic pCa by injecting 100 mM-EGTA before or after cyclic GMP fails to alter the magnitude of the response to the nucleotide. Enrichment of the fibre with Mg2+ at the time of injection of cyclic GMP leads to a reduced response. No change in response, however, is seen when the internal free Mg concentration is suddenly reduced by injecting 0.05 M-pyrophosphate with cyclic GMP. 5. Injection of cyclic GMP-dependent protein kinase stimulatory modulator before cyclic GMP fails to enhance the response to the nucleotide. The same is true of the phosphodiesterase inhibitor protein. However pre-injection of 10(-2) M-papaverine enhances the response to a subsequent injection of 10(-3) M-cyclic GMP. 6. Injection of pure protein kinase inhibitor (1.6 x 10(-4) M) before 10(-3) M-cyclic GMP reduces the response to the nucleotide. 7. The argument is put forward that injected cyclic GMP stimulates the ouabain-insensitive Na efflux mainly by activating cyclic AMP-protein kinase rather than cyclic GMP-proton kinase.
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PMID:Stimulation by cyclic GMP of sodium efflux in barnacle muscle fibres. 4 Oct 90

The activity of the phosphodiesterase enzyme(s) responsible for the degradation of cylic adenosine monophosphate (CA.M.P.) and cyclic guanosine monophosphate (CG.M.P. (in human normal and carcinomatous lung tissue has been investigated. Enzyme activities were 3-5 times greater in normal than in carcinomatous lung. This is compatible with the known higher concentrations of these cyclic nucleotides in normal tissues. It is suggested that cancer chemotherapy designed to block the phosphodiesterase activity, and thus promote accretion of CA.M.P and CG.M.P., may provide a means of normalising cancerous tissue. Both phosphodiesterase activities in both types of tissue were inhibited by methylxanthines at 10(-3) mol/l, but some enzyme potentiation was observed at lower concentration.
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PMID:Cyclic nucleotide phosphodiesterase activity of human normal and carcinomatous lung tissue. 6 44

The antiallergy drugs, cromolyn sodium and lodoxamide tromethamine (U-42,585E) show in vitro dose responses which are bell-shaped or biphasic in mast cells. The nature of the biphasic dose response is poorly understood; however, through the use of specific antagonists, it has been possible to show that at the high concentrations of these drugs leading to enhanced histamine release or multiple high-dose tachyphylaxis, a cholinergic receptor is stimulated in the cell. This receptor is muscarinic in nature and can be blocked by atropine or quinuclidinyl benzilate (QNB). Prevention of multiple dose tachyphylaxis to either drug can be modulated by pretreatment with atropine or QNB. High concentrations of both drugs cause the cell accumulation of cyclic-guanosine monophosphate through stimulation of guanyl cyclase and prevention of cGMP breakdown by inhibition of the phosphodiesterase (PDE) for cGMP.
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PMID:Development of new antiallergic drugs (cromolyn sodium, lodoxamide tromethamine). What is the role of cholinergic stimulation in the biphasic dose response? 9 55


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