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 increased motor activity of reserpine-nialamide pretreated rats given dopamine into the nucleus accumbens was potentiated in a dose-dependent manner by systemically administered caffeine. Similarly, the increase in motor activity seen when the endogenous dopamine was released by intraperitoneally administered amphetamine was potentiated by systemically given caffeine. These effects might be due to an increase in the dopamine-induced accumulation of cyclic AMP in the nucleus accumbens after inhibition of the phosphodiesterase by caffeine.
J Pharm Pharmacol 1975 Sep
PMID:Locomotor activity stimulation in rats produced by dopamine in the nucleus accumbens: potentiation by caffeine. 24 10

Unlike asthmatics, healthy persons are relatively unresponsive to airway constrictors. By using partial expiratory flow-volume (PEFV) curves the authors have demontrated, in healthy subjects, dose-related decreases in flow rates following challenge with histamine and methacholine aerosols. With the use of semilogarithmic dose-response curves they have shown that 80 mg oral propranolol augmented, whereas oral pretreatment with 400 mg W10294A (an experimental bronchodilator) decreased, histamine and methacholine-induced airway constriction. However, 300 mg of orally administered aminophylline failed to modify the airway constrictor effects of histamine and methacholine. Moreover, variation was noted in induced airway constriction in healthy subjects with decreases in flow rates being greater in the morning than in the afternoon. The authors conclude that (1) propranolol augments whereas theophylline fails to prevent nonspecific induced airway constriction in healthy subjects. This suggests that the bronchodilator action of theophylline may be unrelated to its phosphodiesterase inhibitory activity, (2) control of volume history, by use of partial expiratory flow-volume curves, is useful in quantifying pharmacologic protection and augmentation of nonspecific induced airway constriction in healthy subjects and (3) conclusions resulting from observations of induced airway constriction in healthy subjects may be dependent upon the effects of diurnal variation.
Ann Allergy 1979 Sep
PMID:Modification of induced airway constriction in healthy subjects. 47 62

1. Arrhenius plots of the glucagon-stimulated adenylate cyclase, 5'-nucleotidase, (Na+ + K+)-stimulated adenosine triphosphatase and Mg2+-dependent adenosine triphosphatase activities of control hamster liver plasma membranes exhibited two break points at around 25 and 13 degrees C, whereas Arrhenius plots of their activities in hibernating hamster liver plasma membranes exhibited two break points at around 25 and 4 degrees C. 2. A single break occurring between 25 and 26 degrees C was observed in Arrhenius plots of the activities of fluoride-stimulated adenylate cyclase, basal adenylate cyclase and cyclic AMP phosphodiesterase of liver plasma membranes from both control and hibernating animals. 3. Arrhenius plots of phosphodiesterase I activity showed a single break at 13 degrees C for membranes from control animals, and a single break at around 4 degrees C for liver plasma membranes from hibernating animals. 4. The temperature at which break points occurred in Arrhenius plots of glucagon- and fluoride-stimulated adenylate cyclase activity were decreased by about 7--8 degrees C by addition of 40 mm-benzyl alcohol to the assays. 5. Discontinuities in the Arrhenius plots of 4-anilinonaphthalene-1-sulphonic acid fluorescence occurred at around 24 and 13 degrees C for liver plasma membranes from control animals, and at around 25 and 4 degrees C for membranes from hibernating animals. 6. We suggest that in hamster liver plasma membranes from control animals a lipid phase separation occurs at around 25 degrees C in the inner half of the bilayer and at around 13 degrees C in the outer half of the bilayer. On hibernation a change in bilayer asymmetry occurs, which is expressed by a decrease in the temperature at which the lipid phase separation occurs in the outer half of the bilayer to around 4 degrees C. The assumption made is that enzymes expressing both lipid phase separations penetrate both halves of the bilayer, whereas those experiencing a single break penetrate one half of the bilayer only.
Biochem J 1978 Sep 15
PMID:Changes in the form of Arrhenius plots of the activity of glucagon-stimulated adenylate cyclase and other hamster liver plasma-membrane enzymes occurring on hibernation. 72 95

The ts CB1200 (antimutator) mutation in bacteriophage T4 DNA polymerase increases the accuracy of DNA replication since it results in a decrease in the frequency of mutations in other phage genes. The CB120 polymerases differs from the wild type enzyme in the slow rate at which it copies templates where primer extension requries displacement of polynucleotides base-paired to the template strand, even in the presence of the T4 DNA unwinding protein (gene 32-protein). The ratio of nucleotides turned over (DNA-dependent conversion of deoxynucleoside triphosphate to deoxynucleoside monophosphate) to nucleotides stably incorporated into product is 10 to 100 times higher with the mutant than wild type enzyme, depending on the DNA used as the template. This high turnover rate may increase the efficiency of removal of noncomplementary nucleotides by the antimutator enzyme and is in agreement with the findings of Muzyczka et al, (Muzyczka, N., Poland, R. L., and Bessman, M. J. (1972) J. Biol, Cehm. 247, 7116-7122) with the L141 and L42 antimutator T4 DNA polymerases. Since the 3'- to 5'-exonuclease activity of the CB120 mutant polymerase is not higher than that of the wild type enzyme, it is suggested that the high turnover rate may result from increased opportunity to remove newly incorporated nucleotides due to the slow rate at which the mutant enzyme moves to the next template nucleotide. In the accompanying paper we show that the CB120 antimutator polymerase also initially selects incorrect nucleotides for incorporation less frequently than the wild type enzyme. Thus this antimutator polymerase appears to have both greater accuracy in nucleotide selection and an enhanced ability to remove incorrect nucleotides.
J Biol Chem 1976 Sep 10
PMID:Control of mutation frequency by bacteriophage T4 DNA polymerase. I. The CB120 antimutator DNA polymerase is defective in strand displacement. 95 82

Mouse L Cells, grown in suspension culture can be rendered permeable to exogenous deoxynucleoside triphosphates by a cold shock in a near isotonic buffer system. These cells use the deoxynucleotides to synthesize DNA in a semiconservative fashion. The addition of 0.05% Triton X-100 to this system increases the permeability of the cells so that exogenously supplied macromolecules gain access to the DNA. When DNAase and phosphodiesterase are added to the detergent-permeabilized cells, the cell DNA is rapidly degraded, demonstrating that the enzymes reach the DNA within the first 2 min of the incubation period. Addition of whole calf thymus histone or histone fractions to the detergent-permeabilized cells inhibits DNA synthesis. The lysine-rich histone, F is a more effective inhibitor than the arginine-rich histone, F3. The other histone fractions including the slightly lysine-rich fractions, F2a and F2b, are intermediate between F1 and F3 as inhibitors of DNA- synthesis. Kinetic analysis demonstrates that the added histones increase apparent Km and reduce V of DNA synthesis in the permeabilized cells. These studies suggest the possibility that histones alter the association of the DNA replication complex and the DNA template in a manner that reduces the rate of DNA synthesis.
Biochim Biophys Acta 1976 Sep 20
PMID:Histone inhibition of DNA synthesis in eukaryotic cells permeable to macromolecules. 96 82

Out of 17 enzymes studied, only 9 were detectable by starch gel electrophoresis in mouse neuroblastoma cells in culture. Prostaglandin E1 (PGE1) and 4(-3-butoxy-4-methoxybenzyl)-2-imidazolidinone (R020-1724), a specific inhibitor of cAMP phosphodiesterase, were used to induce "differentiation". Lactate and 6-phosphogluconate dehydrogenases and adenylate kinase were expressed as single bands in untreated neuroblastoma and induced "differentiated" cells, but the electrophoretic mobility of these enzymes in PGE1-treated cells was slower than that in malignant and R020-1724-treated cells. Three bands of glucose 6-phosphate dehydrogenase were detectable in PGE1-treated cells, whereas the R020-1724-treated cells had two bands and the untreated neuroblastoma cells had only one band. Aldolase was also expressed as a single band; however, the activity of this enzyme was much higher in PGE1-treated cells, whereas the activity was bately detectable for R020-1724-treated and untreated neuroblastoma cells. Some of the enzymes which are present in vivo are absent in vitro. Alkaline phosphatase is present in brain but is absent in neuroblastoma cells in vivo and in vitro. Two bands each of triose phsophate isomerase, fumarase and aldolase are present in brain, but only one band of these enzymes is present in neuroblastoma cells. Although PGE1 and R020-1724 induce many differentiated functions in neuroblastoma cells in a similar manner, PGE1 appears to change characteristically the expression of several enzymes.
Br J Cancer 1976 Sep
PMID:Altered enzyme expression in "differentiated" murine neuroblastoma cells. 97 99

Trapidil increases the isoprenalin-induced necrosis of the myocardium in the rat. In the paper is referred to the importance of the term of application in relation to the application of the infarcting noxa. Trapidil has a particularly unfavourable effect, if it is given after isoprenalin. The shift of the relation from the oxygen requirement to the oxygen supply by beta-adrenergic stimulation is regarded as an equivalent for the acute ischaemia. The authors see a connection between the phosphodiesterase-inhibiting activity of trapidil and the influence of the size of necrosis after the application of isoprenalin in the rat. These findings have also clinical importance, as the area of indication explicitly includes the application after fresh myocardial infarction and in acute pectanginous attack.
Z Gesamte Inn Med 1976 Sep 15
PMID:[Modification of the isoprenaline-induced myocardial necrosis using trapidil]. 100 38

Lipid droplets isolated from rabbit renal medullary tissue were analyzed and found to be composed of triglyceride and free fatty acids in a ratio of 2.9:1. These triglycerides were unique when compared to triglycerides of other rabbit tissues examined, in that they contained high percentages of octadecanoic acid (stearic acid, 9.8%), 5,8,11,14-eicosatetraenoic acid (arachidonic acid, 6.8%), and 7,10,13,16-docosatetraenoic acid (adrenic acid, 10%). Lipid droplet triglycerides were found to increase during experimental hydronephrosis and after administration of indomethacin, a prostaglandin synthetase and phosphodiesterase inhibitor. From gas liquid chromatography of fatty acid methyl esters of these triglycerides, it was determined that they were enriched further in their percent composition of 9,12-octadecadienoic acid (linoleic acid) and arachidonic acid, a prostaglandin precursor. The inverse relationship between lipid droplets and prostaglandin content in the inner medulla suggested a significant role of lipid droplet triglycerides as storage pools for prostaglandin precursors.
Lipids 1975 Sep
PMID:Analyses of renal medullary lipid droplets from normal, hydronephrotic, and indomethacin treated rabbits. 117 69

The lysosomal stabilizer and anti-malarial agent, chloroquine, stimulated the respiration and motility of fresh and aged bovine spermatozoa stored in vitro. Duplication of these effects by the phosphodiesterase inhibitors, theophylline and caffeine, suggested that enhancement of sperm activity by chloroquine may be mediated by cyclic AMP.
J Reprod Fertil 1975 Sep
PMID:Stimulatory effect of the lysosomal stabilizer, chloroquine, on the respiration and motility of fresh and aged bovine spermatozoa. 118 15

The present study investigated the effects of celiprolol a novel beta 1-antagonist with partial beta 2-agonist activity on the human failing heart. Experiments were performed on isolated electrically driven atrial and ventricular cardiac preparations and in membrane preparations from the left ventricles of nine patients (four with dilated cardiomyopathy; five with ischemic cardiomyopathy) undergoing cardiac transplantation for terminal heart failure. Celiprolol produced a negative inotropic effect in atrial and ventricular heart muscle. However, in the presence of forskolin--which activates the catalyst of the adenylate cyclase-or the cAMP phosphodiesterase inhibitor milrinone, celiprolol produced concentration-dependent positive inotropic effects and positive lusitropic effects. Experiments with the beta 1-and beta 2-selective antagonists CGP 207.12A and ICI 118.551, respectively, suggest that the positive inotropic response is mediated by beta 2-adrenoceptors. In radioligand binding experiments, a selectivity of 15.7 [-Gpp(NH)p] or 23.9 [+Gpp(NH)p] as judged from the Ki values--of binding to beta 2-adrenoceptors was measured in the failing human ventricular myocardium. Competition curves with celiprolol alone and in the presence of the guanine nucleotide Gpp(NH)p revealed no evidence for agonist activity at beta 1- or beta 2-adrenoceptors. It is concluded that amplification of the cAMP response is able to unmask partial agonist activity of celiprolol in the failing human heart at beta 2-adrenoceptors. The inotropic measurements are a more sensitive approach than radioligand binding studies. Whether the pharmacological profile of celiprolol will be useful in conditions like heart failure is questionable with respect to the potential downregulation of beta 2-adrenoceptors by its partial agonist activity.
J Cardiovasc Pharmacol 1992 Sep
PMID:Positive inotropic effects due to partial agonistic activity of the beta-adrenoceptor antagonist celiprolol following amplification of cAMP formation in failing human myocardium. 127 96


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