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)

Adenosine, AMP, ADP and ATP activated adenylate cyclase in pig skin (epidermis) slices resulting in the accumulation of cyclic AMP. This effect was highly potentiated by the addition of the cyclic AMP-phosphodiesterase inhibitor, papaverine. But another inhibitor, theophylline, strongly blocked the activation of adenylate cyclase by adenosine and adenine nucleotides. Theophylline apparently competed with adenosine for the cell surface receptor. Like theophylline, the addition of adenine alone caused no accumulation of cyclic AMP, but it significantly inhibited the stimulatory effect of adenosine. Guanosine, or guanine, cytidine, uridine, or thymidine nucleotides had no effect on the accumulation of cyclic AMP. Among other adenine nucleotides we tested, adenosine 5'-monophosphoramidate, but not adenosine 5'-monosulfate significantly increased cyclic AMP especially with the addition of papaverine. Neither 2'- nor 3'-adenylic acid were effective. Our data indicate that pig epidermis has four specific and independent adenylate cyclase systems for adenosine (and adenine nucleotides), histamine, epinephrine and prostaglandin E.
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PMID:Adenosine and adenine nucleotides stimulation of skin (epidermal) adenylate cyclase. 18 2

The influence of various cyclic nucleotides on in vitro haemoglobin synthesis has been examined in suspension cultures of mammalian marrow cells. Over a wide range of concentrations, dibutyryl cyclic AMP (db-cAMP) was either ineffective or inhibited haemoglobin synthesis by marrow cells from rat, mouse and guinea-pig. However, 10(-3) M db-cAMP consistently stimulated haemoglobin synthesis in cultures of human, sheep, rabbit and canine cells, with the latter being most responsive. This effect, which approached in magnitude that of erythropoietin (ESF) itself, was specific for cAMP and its mono- and dibutyryl derivatives and was not inhibited by anti-ESF. Adenosine, AMP, ADP, ATP, cGMP, db-cGMP, cCMP, cIMP and sodium butyrate were either inactive or inhibitory at similar concentrations. Enhancement of haemoglobin synthesis was also observed with the phosphodiesterase inhibitor, RO-20-1724. The susceptibility to ionizing radiation of the response to ESF and db-cAMP was marked, indicating that the increased haemoglobin synthesis in this system was proliferation dependent, although the response to db-cAMP was less radiosensitive. Studies with tritiated thymidine showed that about 50% of the cells which were responding to either db-cAMP or ESF were actively engaged in DNA synthesis. However, the physical characteristics of db-cAMP-and ESF-responsive cells were dissimilar as analysed by their velocity sedimentation properties. These studies demonstrate that cAMP has a major stimulatory effect on haemoglobin synthesis with cells from selected mammalian species with activity approaching that of ESF, but the target cells most responsive to these agents appear different. The results suggest that cyclic nucleotide-related mechanisms may modulate in vitro erythropoiesis.
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PMID:Studies of the influence of cyclic nucleotides on in vitro haemoglobin synthesis. 19 63

With a view of decoding the mechanisms of their action the effect of papaverine, chlorpromazine and imipramine produced on a number of blood platelets hemostatic functions was studied. All the three drugs suppress in a characteristic fashion the aggregation on blood platelets caused by thrombin in the Tyrode solution and in a plasma defibrilated by heating, as well as by collogen and ADP in the citrated plasma. Unlike chlorpromazine and imipramine papaverine exerts a strong inhibiting action on the phosphodiesterase activity. Chlorpromazine and imipramine suppress the absorption of serotonin and retraction more intensively than this is done by papaverine and call forth morphological changes in the blood platelets that proceed parallel with changes in the intensity of the photodiffusion and liberation of endogenous serotonin. It is postulated that chlorpromazine and imipramine manifest their inhibitory effect through nonspecific damage of the blood platelets membranes, whereas papaverine does this through exchange of adenine-nucleotides and, especially, of 3',5'-AMP.
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PMID:[Comparative effect of chlorpromazine, imipramine and papaverine on the blood platelet function]. 19 25

Mammalian erythropoiesis, as assayed by erythroid colony formation in vitro, is enhanced by cyclic adenosine nucleotides and agents which are capable of raising intracellular cyclic AMP (cAMP) levels. With canine marrow cells as target, this enhancement was shown to be specific for cAMP and its mono- and dibutyryl derivatives. Adenosine and its derivatives, such as AMP, ADP and ATP, and other cyclic nucleotides, such as cGMP, dibutyryl-cGMP, cCMP and cIMP and sodium butyrate were inactive. The phosphodiesterase inhibitor, RO-20-1724, and the adenyl cyclase stimulator, cholera enterotoxin, both markedly increased colony numbers. Studies with tritiated thymidine showed that about 50% of the cells responding to either erythropoietin (ESF) or dibutyryl cAMP (db-cAMP) were in DNA synthesis. However, by unit gravity sedimentation velocity analysis, the peak of ESF-responsive colony forming cells sedimented more rapidly (8-7 +/- 0-2 mm/hr) than the peak of db-cAMP-responsive cells (7-5 +/- 0 mm/hr). These results demonstrate that adenyl cyclase-linked mechanisms influence in vitro erythropoietic proliferation and suggest that other hormones and simple molecules might interact with surface receptors and thus modulate the action of ESF at the cellular level.
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PMID:Modulation of in vitro erythropoiesis: enhancement of erythroid colony growth by cyclic nucleotides. 19 98

Although roles of roles of cyclic AMP and cyclic GMP in platelets are though to be important on platelet aggregation, little information on their phosphodiesterase (PDE) is available. Cyclic AMP and cyclic GMP hydrolytic activities of platelets (cAMPPDE and cGMPPDE in platelets) and platelet aggregation by ADP and adrenaline were measured in 22 healthy volunteers, 26 arteriosclerotic patients and other 20 miscellaneous patients excluding vascular diseases. Activities of cAMPPDE and cGMPPDE of platelets were 2.37 +/- 0.52, 7.23 +/- 1.84 in the healthy, 2.50 +/- 0.85, 7.53 +/- 2.60 in the arteriosclerotics and 2.38 +/- 1.02, 6.98 +/- 2.59 pmol/min/10(7) platelets in the miscellaneous patients, respectively. No significant difference was observed among these three groups. Platelet aggregabilities also showed no significant difference. However, there was a significant inverse correlation between the aggregability by 1 microgram/ml of adrenaline and the PDE activities only in the arteriosclerotic patients. The correlation coefficient were-0.61 between the primary aggregation and cAMPPDE,-0.65 between the primary aggregation and cGMPPDE,-0.58 between the 5 min aggregation and cAMPPDE and -0.76 between the 5 min aggregation and cGMPPDE. The inverse correlation between platelet aggregation and cyclic nucleotide metabolism in circulating platelts of the arteriosclerotic patients may suggest that interaction of platelets with arteriosclerotiv vessel walls would produce a certain change in platelets.
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PMID:Platelet aggregation and cyclic nucleotide phosphodiesterase activity in arteriosclerotic patients. 20 71

The cyclic AMP-phosphodiesterase (EC 3.1.4.17) of buffalo spermatozoa is distributed in the head, mid-piece and tail fractions and has multiple forms, 70% of which is in the bound form. The bound enzyme was not solubilized by Triton X-100, lubrol or hyamine 2389. Kinetic measurements of the soluble enzyme showed two apparent Km values for low and high cAMP concentrations, i.e. 4.5 and 100 micro M with Vmax values of 0.25 and 2.0 nmol cAMP hydrolysed min-1 mg protein-1. The bound enzyme had an apparent Km of 66.6 microM with a Vmax of 0.75 nmol cAMP hydrolysed min-1 mg protein-1. The pH for optimum enzyme activity was 7.5 and Mg2+ was essential for the activity of the soluble and bound enzymes. Methylxanthines, ATP, ADP and ppi inhibited the soluble and bound enzymes, ATP being the most potent inhibitor.
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PMID:Adenosine 3'5'-monophosphate phosphodiesterase of buffalo spermatozoa. 22 88

The regulatory role of cyclic nucleotide phosphodiesterase(s) and cyclic AMP metabolism in relation to progesterone production by gonadotropins has been studied in isolated rat ovarian cells. Low concentrations of choriogonadotropin (0.4-5ng/ml) increased steroid production without any detectable increase in cyclic AMP, when experiments were carried out in the absence of phosphodiesterase inhibitors. The concentration of choriogonadotropin (10ng/ml) that stimulated progesterone synthesis maximally resulted in a minimal increase in cyclic AMP accumulation and choriogonadotropin binding. Choriogonadotropin at a concentration of 10ng/ml and higher, however, significantly stimulated protein kinase activity and reached a maximum between 250 and 1000ng of hormone/ml. Higher concentrations (50-2500ng/ml) of choriogonadotropin caused an increase in endogenous cyclic AMP, and this increase preceded the increase in steroid synthesis. Analysis of dose-response relationships of gonadotropin-stimulated cyclic AMP accumulation, progesterone production and protein kinase activity revealed a correlation between these responses over a wide concentration range when experiments were performed in the presence of 3-isobutyl-1-methylxanthine. The phosphodiesterase inhibitors papaverine, theophylline and 3-isobutyl-1-methylxanthine each stimulated steroid production in a dose-dependent manner. Incubation of ovarian cells with dibutyryl cyclic AMP or 8-bromo cyclic AMP mimicked the steroidogenic action of gonadotropins and this effect was dependent on both incubation time and nucleotide concentration. Maximum stimulation was obtained with 2mm-dibutyryl cyclic AMP and 8-bromo cyclic AMP, and this increase was close to that produced by a maximally stimulating dose of choriogonadotropin. Other 8-substituted derivatives such as 8-hydroxy cyclic AMP and 8-isopropylthio cyclic AMP, which were less susceptible to phosphodiesterase action, also effectively stimulated steroidogenesis. The uptake and metabolism of cyclic [(3)H]AMP in ovarian cells was also studied in relation to steroidogenesis. When ovarian cells were incubated for 2h in the presence of increasing concentrations of cyclic [(3)H]AMP, the radioactivity associated with the cells increased almost linearly up to 250mum-cyclic [(3)H]AMP concentration in the incubation medium. The (3)H label in the cellular extract was recovered mainly in the forms ATP, ADP, AMP, adenosine and inosine, with cyclic AMP accounting for less than 1% of the total tissue radioactivity. Incubation of cyclic AMP in vitro with ovarian cells resulted in a rapid breakdown of the nucleotide in the medium. The degradation products in the medium have been identified as AMP, adenosine and inosine. The rapid degradation of cyclic AMP by phosphodiesterase(s) makes it difficult to correlate changes in cyclic AMP concentrations with steroidogenesis. These observations thus provide an explanation for the previously observed lack of cyclic AMP accumulation under conditions in which low doses of choriogonadotropin stimulated steroidogenesis without any detectable changes in cyclic AMP accumulation.
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PMID:Receptor-mediated gonadotropin action in the ovary. Regulatory role of cyclic nucleotide phosphodiesterase(s) in intracellular adenosine 3':5'-cyclic monophosphate turnover and gonadotropin-stimulated progesterone production by rat ovarian cells. 22 66

1-Propyl-3-methyl-7-(5-hydroxy-hexyl)-xanthine (HWA 153) is a new bronchospasmolytic agent with a significant influence on the cAMP system of lungs and bronchi. In in vitro experiments HWA 153 inhibits cAMP phosphodiesterase (PDE) isolated from bovine bronchi more than does theophylline. HWA 153 is (in conc. 5 x 10(-4) mol/l) 1.8 and 4.3 times more active as a PDE inhibitor of guinea pig lungs and bronchi, respectively, than theophylline-ethylenediamine. HWA 153 also stabilizes rat erythrocyte membrane against hypoosmotic shock. In isolated guinea pig bronchi HWA 153 (in conc. 5 x 10(-4) mol/l) decreases by 77% bronchial spasm induced by the addition of histamine (5 x 10(-5) mol/l). A significant increase in cAMP level of bronchi was simultaneously observed. In in vivo experiments HWA 153 (25 mg/kg p.o.) inhibits PDE of lungs and bronchi of guinea pigs. Simultaneously, a significant increase in cAMP level in these organs was observed. In in vivo experiments with hypoxic rats, HWA 153 (25 mg/kg p.o.) increases ATP, ATP/ADP ratio and adenylate energy charge (AEC) in hypoxic rats, 1 h after administration. This indicates a positive influence of HWA 153 on the energy metabolism of red blood cells.
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PMID:On the biochemical mechanism of action of 1-propyl-3-methyl-7-(5-hydroxy-hexyl)-xanthine (HWA 153), a new bronchospasmolytically active methyl xanthine derivative. 22 4

Isolated plasma membranes from mouse fibroblast lines 3T3 and its tranformant SV-3T3 contain a phosphodiesterase (oligonucleotidase, E.C. 3.1.4.19; nucleotide pyrophosphatase, E.C. 3.6.1.9) that splits capped and methylated messenger RNA obtained from both reovirus and vesicular stomatitis virus. The isolated membranes are free of demonstrable ribonuclease activity and split the mRNA to produce 7-methyl guanosine diphosphate as a product. With ATP as substrate for the phosphodiesterase enzyme, the product is AMP. Synthetic caps, AMP, ADP and ATP, but not cyclic AMP, can compete with the substrate p-nitrophenyl thymidilic acid. A possible regulatory role on messenger translation is proposed.
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PMID:Uncapping of viral messenger RNA by phosphodiesterase of fibroblast plasma membranes. 22 44

Prostacyclin (PGI2) infused intravenously into anaesthetized rabbits inhibited electrically-induced thrombus formation in the carotid artery, increased bleeding time and inhibited ex vivo platelet aggregation induced by ADP or arachidonic acid. The increase in bleeding time and the inhibition of ex vivo platelet aggregation lasted for as long as the infusion of PGI2 was maintained but rapidly disappeared after infusion was stopped. Prostacyclin is a more potent inhibitor of platelet function, in vivo than prostaglandin E1 (PGE1) or prostaglandin D2 (PGD2). The effects of prostacyclin on all parameters studied except blood pressure were potentiated by the concomitant administration of theophylline, a phosphodiesterase inhibitor.
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PMID:The effect of prostacyclin (PGT2) on platelet behaviour. Thrombus formation in vivo and bleeding time. 38 34


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