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)

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

Anthopleurin-A (AP-A), a polypeptide with MW ca. 5500 (53 amino acids), isolated from the sea anemone, Anthopleura xanthogrammica (Brandt), elicited a potent positive inotropic effect but without an accompanying chronotropic effect on the isolated cardiac muscles of rat, rabbit, guinea pig and cat. Similarly in dogs and cats in situ, i.p. injections of AP-A increased the contractile force without effect on heart rate or blood pressure. The cardiotonic potency for AP-A was equivalent to that of isoproterenol but much greater than that for ouabain or glucagon on the isolated cardiac muscle. AP-A increased the contractile force (cardiac output) and decreased atrial pressure in dog heart during pentobarbital-induced failure. This inotropic effect was not inhibited by propranolol pretreatment. The Ca++ requirement to restore the contractile force was less in AP-A-treated than in ouabain or isoproterenol-treated tissues. After AP-A treatment, the cardiac contractility was more resistant to hypoxia and to low or high temperature stress than ouabain-treated or control preparations. AP-A at 5 10(-9) M increased the duration of the action potential, its mean rate of rise and conduction in the guinea-pig atria and ventricles. At the maximum effective concentration, AP-A did not inhibit Na+, K+-activated adenosine triphosphatase, phosphodiesterase (high Km and low Km) and cyclic 3',5'-adenosine monophosphate content of guinea-pig heart. AP-A (5 X 10(-8) to 5 X 10(-7) M) neither contracted nor relaxed the isolated vascular smooth muscle. The results suggest that AP-A may be useful in the clinical management of cardiac failure and as an experimental tool to study the pharmacology and physiology of cardiac muscle.
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PMID:A polypeptide (AP-A) from sea anemone (Anthopleura xanthogrammica) with potent positive inotropic action. 1 Apr 26

Whereas extracellular calcium is absolutely required for neurotransmitter release consequent to stimulation of adrenergic and other neurons, a large number of substances are known to modify the amount of norepinephrine released per nerve impulse. In general, cyclic nucleotides, phosphodiesterase inhibitors, beta-adrenoceptor agonists, cholinergic nicotinic agonists, and angiotensin are able to enhance neurally mediated norepinephrine release, whereas alpha-adrenoreceptor agonists, cholinergic muscarinic agonists, prostaglandins of the E series, opiates, enkephalins, dopamine, and adenosine inhibit neurally mediated norepinephrine release. Although it has been proposed that cyclic AMP may enhance, and endogenous cyclic GMP may inhibit, neurotransmitter release, no consistent relationship between the effects of the several modulators of neurally mediated norepinephrine release and their effects on adenylate and guanylate cyclase is as yet apparent. The demonstration of whether such a relationship exists must await the development of techniques that will allow the measurement of cyclic nucleotide levels in the presynaptic adrenergic nerve terminal after exposure to the putative modulators of release and consequent to nerve stimulation.
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PMID:Multiple factors regulating the release of norepinephrine consequent to nerve stimulation. 3 4

Effects of parathyroid hormone (PTH) upon cyclic AMP and calcium efflux in isolated renal cortical tubules from hamsters were investigated. PTH caused a rapid rise in cyclic AMP levels, temporally preceding an increase in calcium efflux. Increases in both cyclic AMP levels and calcium efflux were noted over an identical PTH concentration range 0.007--0.7 U/ml). Other peptide hormones tested which had no effect upon cyclic AMP levels did not enhance efflux of calcium. The phosphodiesterase inhibitor methyl isobutylxanthine (MIX) was utilized in other studies to potentiate the cyclic AMP response, and produce a range of cyclic AMP concentrations in response to PTH. In these experiments a range of calcium efflux responses was noted which closely paralleled changes in cyclic AMP. Direct addition of cyclic AMP or dibutyryl cyclic AMP to isolated renal tubules caused increased efflux of calcium, while addition of 5'-AMP did not. These results indicate a role for cyclic AMP as a mediator of PTH-induced calcium efflux in this system and suggest that cyclic AMP may mediate the action of this hormone in enhancing renal conservation of calcium in vivo.
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PMID:Parathyroid hormone-induced calcium efflux from isolated renal cortical tubules: evidence for cyclic AMP mediation. 9 Jun 29

The concentration of cyclic AMP (cAMP) and its metabolites (5'-AMP and adenosine) as well as the adenyl cyclase, cAMP phosphodiesterase, and 5'-nucleotidase activities were determined in lymphocytes of thymus, spleen, and lymph nodes of control and protein-deficient rats. The values of these parameters, when expressed as per milligran DNA and as per 10-8 cells, but not always when expressed as per milligran protein, were much lower in the thymus as compared with the spleen and the lymph nodes in the control rats. The protein-deficient diet increased the nucleotide concentrations in the thymus and spleen lymphocytes on a per milligram DNA basis except those of thymic cAMP, which did not change. The same diet also increased the activities of the enzymes involved in the cAMP metabolism in thymic, splenic, and lymph node lymphocytes. Such a peculiarity could be related to the reduction of the mitotic activity of lymphocytes caused by protein deficiency since an inverse relationship has been reported between this activity and the synthesis of cAMP. On the other hand, it was noted that purified lymphocyte suspensions contained paradoxically higher amounts per cell of DNA, RNA, and protein in the thymus, spleen, and lymph nodes of protein-deficient rats as compared with those of the control rats. However, when the cell preparations were not purified, only the lymph node cells displayed a strong increase in their DNA content. Prolongation of the S phase of the cell cycle in these lymphocytes is suggested.
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PMID:Cyclic AMP metabolism and nucleic acid content in the lymphocytes of the thymus, spleen, and lymph nodes of protein-deficient rats. 16 50

The effects of several cyclic nucleotide analogs and of phosphodiesterase inhibitors on the release of norepinephrine (NE) and dopamine-beta-hydroxylase activity (DBH) by electrical stimulation were studied in the isolated, perfused cat spleen. N-6-butyryl-3',5'-adenosine monophosphate (mbcAMP), 8-methylthio-3',5'-adenosine monophosphate, 8-bromo-3',5'-guanosine monophosphate (8-Br-cGMP) and two potent phosphodiesterase inhibitors: 1-methyl-3-isobutylxanthine and 4-(3-butoxy-4-methoxy-benzyl)-2-imidazolidinone (Ro 20-1724) enhanced the overflow of NE and total H and reduced pressure responses elicited by nerve stimulation. A concomitant outflow of DBH activity was observed in the presence of mbcAMP, 8-Br-cGMP or Ro 20-1724. Synergistic effects on the nerve stimulation-mediated overflow of NE and DBH were obtained with low concentratons of Ro 20-1724 and mbcAMP (5 muM). Adenosine 5'-monophosphate produced a very slight increase in nerve stimulated release of NE and DBH activity in concentrations which inhibited pressor responses considerably. cAMP produced slight inhibition of pressure responses but failed to influence the release of either NE or DBH activity during nerve stimulation. In contrast to the enhanced overflow of NE and DBH activity induced by nerve stimulation, with the exception of Ro 20-1724, the spontaneous release of these substances was not modified by any of the cyclic nucleotide analogs or phosphodiesterase inhibitors examined. This effect of Ro 20-1724 can probably be explained by the ability of this compound to inhibit the activity of monoamine oxidase and therefore reduce the formation of deaminated metabolites. The present results suggest that cyclic nucleotides are not directly responsible for the release of the adrenergic neurotransmitter, but may facilitate the normal process of release by nerve stimulation. Phentolamine, a blocker of the alpha adrenergic receptors, produced a marked increase in the nerve stimulation-mediated overflow of NE, total H and DBH activity and inhibited pressure responses. This effect was several times greater than that produced by either cyclic nucleotide analogs or phosphodiesterase inhibitors. In addition, the effect of phentolamine was not modified by prior treatment with 1-methyl-3-isobutylxanthine or Ro 20-1724, suggesting that the effect of phentolamine is not related to its ability to inhibit phosphodiesterase and is probably not mediated via an increase in cAMP.
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PMID:Release of norepinephrine and dopamine-beta-hydroxylase by nerve stimulation. IV. An evaluation of a role for cyclic adenosine monophosphate. 16 57

Several aspects of the cyclic 3', 5'-adenosine monophosphate system of rat mammary glands were investigated including effects of stage of pregnancy and lactation upon tissue cyclic 3', 5'-adenosine monophosphate amounts and adenyl cyclase, cyclic 3', 5'-adenosine monophosphate phosphodiesterase, and protein kinase activities. Cyclic 3', 5'-adenosine monophosphate decreased at early lactation, and this decrease coincided with an increase in phosphodiesterase activity. Adenyl cyclase activity remained unchanged from late pregnancy to end of lactation. At late pregnancy, activity of protein kinase was about the same as during lactation indicating that increase in protein kinase activities in the glands precedes increases in activities of other major enzymes and the increase in ribonucleic acids in late pregnancy or early lactation. Epinephrine, prolactin, growth hormone, thyroxine, and prostaglandine caused 60, 80, 140, 200, and 270% increases in adenyl cyclase activity in vitro.
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PMID:Changes in the cyclic 3', 5'-adenosine monophosphate system of rat mammary gland during lactation cycle. 16 62

The role of cyclic adenosine 3':5'-monophosphate (cyclic 3':5'-AMP) in the regulation of cell division in lymphocytes obtained from healthy donors and from patients with chronic lymphocytic leukemia (CLL) was investigated by determining the levels of cyclic 3':5'-AMP and glycogen and also the activities of several enzymes that are closely associated with the metabolism of these cellular components. Intracellular levels of cyclic 3':5'-AMP were measured in normal and CLL lymphocytes in nondividing, dividing, and quiescent [after phytohemagglutinin (PHA) addition]states. In normal lymphocytes the levels of cyclic 3':5'-AMP fluctuated throughout the cell cycle after PHA addition, whereas in CLL lymphocytes the levels were approximately 3-fold lower than in normal cells and remained relatively constant before, during, and after mitogenic stimulation. Normal cells contained approximately 3-fold lower levels of glycogen than CLL cells, whereas glycogen phosphorylase activities were increased 2- to 4-fold above those in nondividing cells in normal but not in CLL lymphocytes after stimulation with PHA. Furthermore, cyclic 3':5'-AMP phosphodiesterase activities were higher in CLL lymphocytes than in normal ones. Collectively, these studies demonstrated that (a) the intracellular levels of cyclic 3':5'-AMP differ in these two cell types; (b) the levels of cyclic 3':5'-AMP and glycogen qualitatively correlate with the activities of the enzymes that are related to these components; and (c) an inverse relationship between the levels of cyclic 3':5'-AMP and cell growth exists in mitogen-stimulated lymphocytes from healthy donors but not from patients with CLL. These biochemical differences are presumed to exist between normal and "leukemic" lymphocytes, but alternatively they may reflect normal populations of immunologically distinct lymphocytes.
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PMID:Cyclic adenosine 3':5'-monophosphate levels and activities of related enzymes in normal and leukemic lymphocytes. 16 62

The effects of various adenosine phosphate compounds, theophylline, histamine,a nd metiamide, on steady rates of acid secretion by isolated fundic mucosa of the rabbit were measured by the pH stat method. Cyclic adenosine 3':5'-monophosphate (cyclic AMP), N(6), O(2')-dibutyryl adenosine 3':5'-monophosphate and theophylline increased the rate of acid secretion. Addition of theophylline in a concentration which has no stimulatory effect, reduces the effective concentrations cyclic AMP or histamine required for stimulation of acid secretion. Measurements of lactate, pyruvate, and CO2 appearances indicated that the increases in acid secretory rates were predominantly due to H+ and not organic acid accumulation in the luminal bath-secretion. Metiamide prevented the stimulatory effects of histamine and ATP. However, metiamide did not prevent the stimulatory effects of N(6),9(2')-dibutyryl adenosine 3':5'-monophosphate, theophylline, or 5'-AMP. The results provide further evidence for a role of cyclic AMP in governing the rate of acid secretion by rabbit stomach. The data also are consistent with histamine and ATP (at least in the concentration used) requiring adenylate cyclase activity for stimulation of acid secretion and 5'-AMP inhibiting phosphodiesterase activity.
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PMID:Effects of cyclic adenosine 3':5'-monophosphate and related agents on acid secretion by isolated rabbit gastric mucosa. 16 24

The adenylate cyclase activity of rabbit reticulocytes is localized in the stroma. Rabbit reticulocytes are four times more active than mature erythrocytes in transforming in situ formed [14C] adenosine triphosphate into [14C] cyclic adenosine 3':5'-monophosphate. Similarly, anaemic human red blood cells show higher activity in effecting this transformation. The adenylate cyclase activity is stimulated by epinephrine, 40% in rabbit reticulocytes, and 70-80% in anaemic human RBC but not in erythrocytes. Both the reticulocytes and erythrocytes can bind [14C] epinephrine, but the reticulocytes bind a relatively large amount. A glycogen phosphorylase that can be activated by cyclic adenosine 3':5'-monophosphate is detected only in reticulocytes. Both reticulocytes and erythrocytes contain a phosphodiesterase which can hydrolyse cyclic 3':5'-adenosine monophosphate and which is activated by imidazole and inhibited by methyl xanthines.
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PMID:Loss of epinephrine stimulated synthesis of cyclic adenosine 3':5' monophosphate during maturation of rabbit and human reticulocytes. 16 41


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