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 effects of prostaglandin E2 (PGE2) on cyclic AMP levels in various mouse lymphocyte populations were studied. It was found that spleen cells and thymocytes respond comparably to PGE2. Cortisone treatment abolished the responsiveness in thymocytes. Fractionation of splenic lymphocytes on glass wool columns into subpopulations of bone-marrow derived (B) cells or thymus-derived (T) cells showed that both B and T splenic lymphocytes can respond to PGE2. Lymphocytes or spleen cells cultured for varying periods (24--96 hrs) lose their sensitivity to PGE2 stimulation of cAMP. This "refractoriness" to PGE2 is only partially reversed by incubating lymphocytes with phosphodiesterase inhibitors.
Prostaglandins Med 1978 Dec
PMID:The effects of prostaglandins on cAMP levels in subpopulations of mouse lymphocytes. 21 43

A time-saving protein binding assay for the simultaneous determination of cGMP and cAMP has been adapted for human urine, using [3H]cGMP, [14C]cAMP, protein fractions from calf skeletal and lobster tail muscles and the phosphodiesterase inhibitor SQ 20.009. Recovery, accuracy, and precision are approximately at the 10% limit. Good specificity and no interference were observed with diluted urine samples (10 to 20 times).
J Clin Chem Clin Biochem 1978 Dec
PMID:Time saving protein binding assay for the simultaneous determination of guanosine 3':5'-monophosphate (cGMP) and adenosine 3':5'-monophosphate (cAMP) in human urine. 21 69

A correlation between cyclic AMP (adenosine 3' : 5'-monophosphate) concentration within Leishmania cells and proliferation and transformation is demonstrated. By addition of dibutyryl cyclic AMP and cyclic AMP-phosphodiesterase inhibitors to the culture medium the intracellular level of cyclic AMP was increased. In the presence of 1mM caffeine the level of cyclic AMP accumulated in L. tropica promastigotes from 90 pmoles up to 380 pmoles per 10(9) cells, whereas the proliferation rate decreased to 50%. In the case of L. donovani the transformation of amastigotes to promastigotes was inhibited by addition of dibutyryl cyclic AMP as well as caffeine and papaverine. Especially caffeine (2mM) and papaverine (0.1mM) reduced the transformation rate to less than 5% after 48 h, compared to 35% of the control.
Tropenmed Parasitol 1978 Dec
PMID:Effect of cyclic AMP on transformation and proliferation of leishmania cells. 21 33

1. A heat-stable modulator protein was partially purified from mouse epidermis. The protein stimulated modulator-depleted cyclic AMP phosphodiesterase from bovine brain in the presence of Ca2+. 2. DEAE-cellulose chromatography of epidermal extracts demonstrated the presence of two main phosphodiesterase activities that hydrolysed both cyclic AMP and cyclic GMP. A minor peak was eluted between 0.1 and 0.3 M-sodium acetate and a major peak was eluted between 0.3 and 0.45 M-sodium acetate. 3. Cyclic AMP phosphodiesterase activity eluted at low salt concentrations was markedly activated by the epidermal modulator protein in the presence of Ca2+. Storage of the enzyme led to a decrease in its sensitivity to the protein modulator. 4. Treatment of mouse skin with the tumour promoter 12-O-tetradecanoylphorbol 13-acetate, which leads to an increase in epidermal cyclic nucleotide phosphodiesterase activity, did not alter the amount of modulator present in soluble epidermal extracts. The tumour promoter decreased the amount of modulator extractable from particulate epidermal preparations with Triton X-100.
Biochem J 1978 Dec 15
PMID:Calcium-dependent protein modulator of cyclic nucleotide phosphodiesterases from mouse epidermis. 21 52

1. The effects of changes in the cytoplasmic [NADH]/[NAD+] ratio on the efficacy of glucagon to alter rates of metabolism in isolated rat hepatocytes were examined. 2. Under reduced conditions (with 10mM-lactate), 10nM-glucagon stimulated both gluconeogenesis and urea synthesis in isolated hepatocytes from 48h-starved rats; under oxidized conditions (with 10mM-pyruvate), 10nM-glucagon had no effect on either of these rates. 3. The ability of glucagon to alter the concentration of 3':5'-cyclic AMP and the rates of glucose output, glycogen breakdown and glycolysis in cells from fed rats were each affected by a change in the extracellular [lactate]/[pyruvate] ratio; minimal effects of glucagon occurred at low [lactate]/[pyruvate] ratios. 4. Dose-response curves for glucagon-mediated changes in cyclic AMP concentration and glucose output indicated that under oxidized conditions the ability of glucagon to alter each parameter was decreased without affecting the concentration of hormone at which half-maximal effects occurred. 5. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (0.05 mM) significantly reversed the inhibitory effects of pyruvate on glucagon-stimulated glucose output. 6. For exogenously added cyclic [3H]AMP(0.1 mM), oxidized conditions decreased the stimulatory effect on glucose output as well as the intracellular concentration of cyclic AMP attained, but did not alter the amount of cyclic [3H]AMP taken up. 7. The effects of lactate, pyruvate, NAD+ and NADH on cyclic AMP phosphodiesterase activities of rat hepatocytes were examined. 8. NADH (0.01--1 MM) inhibited the low-Km enzyme, particularly that which was associated with the plasma membrane. 9. The inhibition of membrane-bound cyclic AMP phosphodiesterase by NADH was specific, reversible and resulted in a decrease in the maximal velocity of the enzyme. 10. It is proposed that regulation of the membrane-bound low-Km cyclic AMP phosphodiesterase by nicotinamide nucleotides provides the molecular basis for the effect of redox state on the hormonal control of hepatocyte metabolism by glucagon.
Biochem J 1978 Dec 15
PMID:Responsiveness to glucagon by isolated rat hepatocytes controlled by the redox state of the cytosolic nicotinamide--adenine dinucleotide couple acting on adenosine 3':5'-cyclic monophosphate phosphodiesterase. 21 54

Adipocytes isolated from normal, hypothyroid, and hyperthyroid rats were characterized with respect to their lipolytic activity (assessed by glycerol release) and beta-adrenergic receptors (assessed by binding of (--) [3H]alprenolol). Fat cells from hypo- and hyperthyroid rats showed the same affinity (K = 1.4 X 10(10) M(-1) and binding capacity (N = 1.21 X 10(-13) mol/microgram DNA) toward alprenolol as those from normal animals. Adipocytes from hypothyroid rats were unresponsive to epinephrine in a concentration range of 0.1-10 micron, with moderate responses at higher concentrations; injection of T3 in hypothyroid rats restored lipolytic responsiveness of the adipocytes to normal levels. Quabain (1 mM) inhibited lipolytic responses to epinephrine by 40--45% in normal and hyperthyroid rats; the lipolytic increment due to the hyperthyroid state was uninfluenced by ouabain. The lipolytic refractoriness to epinephrine of hypothyroid adipocytes was restored to normal levels by theophylline (1 mM) or EGTA (1 mM); the theophylline and EGTA effects were not additive, suggesting that they stimulated lipolysis via a common mechanism. Epinephrine-induced lipolysis in all groups was progressively inhibited by increasing concentrations of Ca2+ in the medium. The Ca ionophore, A23187, showed a concentration-dependent inhibitory action. Theophylline (1mM) almost completely overcame the inhibitory action of the ionophore; in the presence of lower concentrations of theophylline, the inhibitory effect of the ionophore was least in hypothyroid and greatest in hyperthyroid fat cells. The findings suggest that the differences in the lipolytic response to epinephrine observed in hyperthyroid, euthyroid, and hypothyroid adipocytes are not due to alterations in the number or affinity of beta-adrenergic receptors nor to a membrane mechanism that might show differential ouabain sensitivity, but may be related to altered cellular Ca2+ concentrations which may indirectly alter cellular phosphodiesterase activity.
Endocrinology 1978 Dec
PMID:Thyroid hormone modulation of epinephrine-induced lipolysis in rat adipocytes: a possible role of calcium. 21 6

Experiments using a phosphodiesterase-minus mutant of Dictyostelium discoideum indicate that ligand-induced loss of cell surface cyclic adenosine 3':5'-monophosphate binding sites (down regulation) can be evoked with concentrations of cyclic adenosine 3':5'-monophosphate as low as 10(-8) M. The loss of receptor sites is observed after 5 min of cell preincubation with cyclic adenosine 3':5'-monophosphate and can be as extensive as 75 to 80%. This decrease in binding sites is correlated with the appearance of a slowly dissociating cyclic adenosine 3':5'-monophosphate binding component. Radioactive cyclic adenosine 3':5'-monophosphate bound to this form of receptor cannot be competed for by nonradioactive cyclic adenosine 3':5'-monophosphate or adenosine 5'-monophosphate and is not accessible to hydrolysis by cyclic adenosine 3':5'-monophosphate phosphodiesterase. The extent of appearance of this binding component is dependent upon the concentration of cyclic adenosine 3':5'-monophosphate used to elicit the down regulation response and the temperature of the incubation medium.
J Biol Chem 1979 Dec 25
PMID:A slowly dissociating form of the cell surface cyclic adenosine 3':5'-monophosphate receptor of Dictyostelium discoideum. 22 1

The effect of several inhibitors of the enzyme cyclic 3',5'-AMP phosphodiesterase as chemoattractants in Physarum polycephalum was examined. Of the compounds tested, 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (Roche 20-1724/001) and 1-ethyl-4-(isopropylidinehydrazino)-1H-pyrazolo-(3,4-b)-pyridine-5-carboxylic acid ethyl ester, hydrochloride (Squibb 20009) were the most potent attractants. 3-Isobutyl-1-methyl xanthine, theophylline, and morin (a flavanoid) were moderate attractants and sometimes gave negative chemotaxis at high concentrations. Cyclic 3',5'-AMP was an effective, but not potent attractant. A repellent effect following the positive chemotactic action was sometimes observed with cyclic 3',5'-AMP at concentrations as high as 1 . 10(-2) M. Dibutyryl cyclic AMP appeared to be a somewhat more potent attractant than cyclic 3',5'-AMP. The 8-thiomethyl and 8-bromoderivatives of cyclic AMP, which are poorly hydrolyzed by the phosphodiesterase, were not attractants in Physarum. Possible participation of cyclic 3',5'-AMP in the directional movement in P. polycephalum is discussed.
Biochim Biophys Acta 1979 Dec 11
PMID:Cyclic 3',5'-AMP phosphodiesterase in Physarum polycephalum. I. Chemotaxis toward inhibitors and cyclic nucleotides. 22 61

The glycogen content of fetal rat lung declines coincident with increased pulmonary phospholipid synthesis. Aminophylline, a methylxanthine cyclic adenosine 3',5' monophosphate (AMP) phosphodiesterase inhibitor, and cyclic AMP augment fetal lung phospholipid synthesis. Because lung glycogen breakdown may contribute to pulmonary phospholipid synthesis, the effects of aminophylline and cyclic AMP on glycogen metabolism were studied in explants of 19 day fetal rat lung in organ culture. Treatment with aminophylline or dibutyryl cyclic AMP for 24 hr, resulted in a 25% (P less than 0.025) and 75% (P less than 0.001) decrease, respectively, in the glycogen content of the explants. Glycogen synthase I activity was reduced by 32% in aminophylline treated cultures (P less than 0.025) and 25% in cyclic AMP treated cultures (P less than 0.025). The percent of total synthase in the active form was significantly reduced in all treated cultures. Neither aminophylline nor cyclic AMP treatment resulted in significant changes in glycogen phosphorylase a or total phosphorylase activity.
Pediatr Res 1979 Dec
PMID:Influence of aminophylline and cyclic AMP on glycogen metabolism in fetal rat lung in organ culture. 23 Apr 47

Both isoproterenol and norepinephrine (NE) increase cyclic AMP in slices of the rat limbic forebrain and the responses are enhanced in the presence of the phosphodiesterase inhibitor RO 20-1724. However, even in the presence of RO 20-1724, no accumulation of cyclic AMP was observed after the addition of dopamine, serotonin or the alpha-agonists methoxamine and phenylephrine. This suggests that these agents do not activate adenylate cyclase in this preparation or that their respective receptors--unlike the beta-receptor--are not coupled to adenylate cyclase. Isoproterenol, which has a high affinity for this adenylate cyclase system but only 20-30% of the maximal activity of NE, does not interfere with the agonist activity of NE. Moreover, the effect of isoproterenol is not additive with that of NE thus suggesting that isoproterenol is acting on a subpopulation of NE receptors. The results indicate that two populations of NE receptors coupled to adenylate cyclase are present in slices of rat limbic forebrain: one which has beta-characteristics and the other with neither alpha- nor beta-characteristics based on agonist studies.
Eur J Pharmacol 1979 Dec 07
PMID:Norepinephrine stimulated cyclic AMP accumulation in rat limbic forebrain slices: partial mediation by a subpopulation of receptors with neither alpha nor beta characteristics. 23 Sep 79


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