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)

Rabbit heart membranes possessing the adenylate cyclase activity were isolated and purified by extraction with high ionic strength solutions and centrifugation in the sucrose density gradient. It was shown that the membranes are characterized by a high percentage of cholesterol (molar ratio cholesterol/phospholipids is 0.24) and an increased activity of Na, K-ATPase, which suggests the localization of adenylate cyclase in the sarcolemma. During centrifugation in the sucrose density gradient the activities of andenylate cyclase and Na,K-ATPase are not separated. Treatment of heart sarcolemma with a 0.3% solution of lubrol WX results in 10--20% solubilization of adenylate cyclase. Purification of the enzyme in the membrane fraction is accompanied by a decrease in the activity of phosphodiesterase; however, about 2% of the heart diesterase total activity cannot be removed from the sarcolemma even after its treatment with 0.3% lubrol WX. Epinephrine and NaF activate adenylate cyclase without changing the pH dependence of the enzyme. The alpha-adrenergic antagonist phentolamine has no effect on the adenylate cyclase activation by catecholamines, glucagon and histamine; the beta-adrenergic antagonist alprenolol competitively inhibits the effects of isoproterenol, epinephrine and norepinephrine, having no effect on the enzyme activation by glucagon and histamine. There is no competition between epinephrine, glucagon and histamine for the binding site of the hormone; however, there may occur a competition between the hormone receptors for the binding to the enzyme. A combined action of several hormones on the membranes results in the averaging of their individual activating effects. When the hormones were added one after another, the extent of adenylate cyclase activation corresponded to that induced by the first hormone; the activation was insensitive to the effect of the second hormone added. It is assumed that the outer membrane of myocardium cells contains a adenylate cyclase and three types of receptors, each being capable to interact with the same form of enzyme. The activity of adenylate cyclase is determined by the type of the receptor, to which it is bound and by the amount of the enzyme-receptor complex.
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PMID:[Isolation, purification and characterization of regulatory properties of adenylate cyclase from rabbit heart]. 2 49

Various receptor-linked cyclic AMP systems were measured in rat neostriatum 2--14 days after selective destruction of neuronal cell bodies and dendrites by micro-injection of 3 microgram of kainic acid. Basal adenylate cyclase activity was reduced by up to 56% in the injected side and the sensitivity to dopamine was abolished. Up to 84% of cyclic nucleotide phosphodiesterase activity, hydrolyzing either cyclic AMP or cyclic GMP, was destroyed by kainic acid injection. Specific binding of [3H]etorphine and [3H]spiroperidol was reduced by up to 62% in the injected side, while non-specific binding was unchanged. All of these changes were time-dependent, and were greatest 7--14 days after kainic acid treatment. On the other hand, intrastriatal kainic acid injection caused no change in the steady-state concentration of cyclic AMP in striatal slices, or in the in vivo cyclic AMP content in the striatum of rats killed by microwave irradiation. Receptor-mediated increases in cyclic AMP accumulation in striatal slices were either unchanged or markedly potentiated by kainic acid treatment. The maximum response to adenosine was unchanged, while the response to isoprenaline was increased up to 3.7-fold, the response to dopamine increased up to 6.7-fold, and the response to PGE1 increased up to 30-fold. The effect of dopamine in kainic acid-treated striatal slices was no longer blocked by fluphenazine, but was blocked by propranolol, suggesting an interaction of dopamine with a beta-adrenoceptor in kainic acid-treated slices. The results suggest differential cellular localizations of the various receptor-linked cyclic AMP systems in rat neostriatum. Some dopamine and opiate receptors, as well as most of the phosphodiesterase activity, are associated with local neuronal elements, while beta-adrenoceptor, adenosine and PGE1 alterations in cyclic AMP are not. The potentiation of the beta-adrenoceptor and PGE1 responses suggests that they may occur in glial cells. In addition, the pool of adenylate cyclase destroyed by kainic acid appears to make little contribution to normal levels of cyclic AMP in the tissue.
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PMID:Receptor-linked cyclic AMP systems in rat neostriatum: differential localization revealed by kainic acid injection. 2 87

Behavioral sensitization of the gill-withdrawal reflex of Aplysia is the result of a prolonged increase in transmitter release from the presynaptic terminals of sensory neurons. Earlier work suggested that this presynaptic facilitation might be mediated by a serotonin-sensitive adenylate cyclase in the sensory neuron terminals. Here we present evidence that presynaptic facilitation results from a cyclic AMP-dependent increase in the calcium current that underlies action potentials in the sensory neurons. The action potentials of sensory neuron cell bodies have, in addition to a sodium current, a calcium current that is enhanced by blocking the opposing potassium current with tetraethylammonium. Under these conditions, the action potentials show a slowly repolarizing plateau that follows the Nernst potential for a calcium electrode and serves as a sensitive assay for changes in calcium current. Stimulation of the pathway that mediates sensitization, incubation with serotonin or phosphodiesterase inhibitors, or intracellular injection of cyclic AMP produces an increase in the calcium plateau in the presence of tetraethylammonium. In addition, both before and after sensitizing stimulation, the duration of the plateau potential parallels transmitter release as measured by the amplitude of monosynaptic excitatory postsynaptic potentials evoked in the motor neurons by intracellular stimulation of single sensory neurons. These results are consistent with the idea that presynaptic facilitation is caused by a cyclic AMP-mediated increase in a voltage-sensitive calcium current in sensory neuron presynaptic terminals. This synaptic action is novel in that it can produce little or no change in the resting potential, is of long duration, and exerts its influence directly on a conductance triggered by the action potential, rather than on non-voltage-sensitive conductances, as is typical of conventional synaptic actions.
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PMID:Presynaptic modulation of voltage-dependent Ca2+ current: mechanism for behavioral sensitization in Aplysia californica. 2 27

Adenylate cyclase activity as well as intracellular content of sAMP were decreased 2.5-4-fold, as compared with normal state, in plasmatic membranes (PM) of hepatoma 22 and of Ehrlich ascites carcinoma--the tumors characterized by high level- of malignancy. Activity of cAMP phosphodiesterase exceeded distinctly the normal value in all the tumors studied. In less malignant hepatoma 48 the adenylate cyclase activity and content of cAMP were similar to those found in normal liver cells. The guanylate cyclase activity did not differ markedly from values found in normal liver cells in PM of all the tumors studied and in liver tissue of the tumor-bearing animals. Distinct alterations were not found in content of cGMP in the tumors, except of hepatomas 60 and 22, in which the nucleotide level exceeded 2-fold the normal value. The ratio cAMP/cGMP was decreased in the most malignant tumors. At the same time, the ratio was distinctly elevated in tumors with the middle level of malignancy (hepatomas 60 and 61).
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PMID:[Concentration of cyclic nucleotides, activity of adenylate cyclase, 3',5'-AMP phosphodiesterase and guanylate cyclase in plasma membranes from liver and hepatomas of different degrees of malignancy]. 3 Feb 12

1. Adenylate cyclase (EC 4.6.1.1) activity has been determined in the parotid and sublingual glands of the mouse. Optimal activity of the enzyme was obtained at a Mg2+-concentration of 8 mM at pH 8.2, using AMP-PNP as the substrate. 2. Cyclic AMP degradation during the adenylate cyclase assay was relatively high in both the homogenate and the 40,000 g pellet-fraction of the glands. Theophylline was effective in inhibiting this degradation only in the parotid hemogenate, whereas isobutylmethylxanthine inhibited the cyclic AMP degradation in both salivary glands. Using the latter phosphodiesterase inhibitor, we observed a higher adenylate cyclase activity in the sublingual glands than in the parotid glands. 3. Various receptor-selective sympathetic and parasympathetic agonists and antagonists have been tested for their capacity to influence the adenylate cyclase activity and the glycoprotein secretion in the parotid and sublingual glands of the mouse, in vitro. (a) The parotid glycoprotein secretion was increased by beta-adrenergic agonists, which stimulate adenylate cyclase, and by cholinergic muscarinic drugs, which do not activate this enzyme. The adrenergic alpha-agonist phenylephrine appeared to be involved neither in the glycoprotein secretion nor in the direct regulation of the adenylate cyclase activity. (b) The sublingual protein and mucin secretion was increased by cholinergic muscarinic agents. The over-all protein secretion was stimulated also by phenylephrine, but this effect could be blocked by propranolol. The adenylate cyclase activity in membrane preparations was not stimulated by these secretogogues.
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PMID:Comparison of adenylate cyclase activity and in vitro secretion in the parotid and sublingual glands of the mouse. 3 65

[3H]Spiperone binding sites and the dopamine-sensitive adenylate cyclase were measured in rat substantia nigra (s. nigra) 7 or 14 days after various lesions. Hemisections, which resulted in a 66% decline in tyrosine hydroxylase and cyclic nucleotide phosphodiesterase and a 73% decrease in glutamate decarboxylase, led to a 50% decrease in [3H]spiperone binding and to the almost complete disappearance of the dopamine-sensitive adenylate cyclase from the s. nigra on the lesioned side. 6-Hydroxydopamine injection into the s. nigra, which depleted tyrosine hydroxylase activity within the s. nigra by 85%, while leaving phosphodiesterase unaffected, resulted in a 40% decrease in [3H]spiperone binding but no change in the dopamine-sensitive adenylate cyclase. Intrastriatal injections of kainic acid did not alter tyrosine hydroxylase activity in the s. nigra, but decreased both glutamate decarboxylase (54%) and phosphodiesterase (68%); [3H]spiperone binding was unaffected by this lesion while the dopamine-sensitive adenylate cyclase was greatly reduced (50-75%). These results suggest that within the s. nigra the dopamine receptor binding sites as defined using [3H]spiperone are located on dopamine neurones while the dopamine-sensitive adenylate cyclase is located presynaptically on striatonigral nerve terminals.
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PMID:Dissociation between the presynaptic dopamine-sensitive adenylate cyclase and [3H]spiperone binding sites in rat substantia nigra. 3 4

An overview of the biochemical events that occur when postsynaptic pineal beta-adrenergic receptors are stimulated is presented. Emphasis is placed on the importance of the adenylate cyclase system for the induction of N-acetyltransferase (NAT). Super- and subsensitive responses of NAT to receptor agonists are related to cAMP concentration, adenylate cyclase and phosphodiesterase activities and receptor binding sites.
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PMID:Studies on the control of pineal indole synthesis: cyclic nucleotides, adenylate cyclase and phosphodiesterase. 3 99

Exposure of the intact astrocytoma cell to isoproterenol not only causes the activation of adenylate cyclase and the accumulation of cyclic AMP but sets in motion a complicated series of events designed to down-regulate the system if exposure to the agonist is extended in time. We have identified at least three of these processes: (1) a rapid uncoupling of the beta-receptor--adenylate cyclase system with subsequent loss of beta-receptors; (2) a slower, nonspecific desensitization of adenylate cyclase to the effects of all classes of receptor agonists by a process that may be mediated by cyclic AMP; and (3) a slow induction of phosphodiesterase activity that is probably mediated by cyclic AMP.
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PMID:Adaptive changes in the responsiveness of adenylate cyclase to catecholamines. 4 42

The accumulation of cyclic adenosine 3',5'-monophosphate (cAMP) in guinea-pig macrophages exposed to the adenylate cyclase (AC) stimulators prostaglandin E1 (PGE1) and isoproterenol (IP), was markedly enhanced by pretreatment of the cells with colchicine, vinblastine, and podophyllotoxin--agents which prevent microtubule assembly. The same agents did not augment basal cAMP levels. The facilitating effect of the drugs on the response to PGE1 and IP developed both in the absence and presence of a phosphodiesterase (PDE) inhibitor. The same drugs also enhanced the accumulation of cAMP induced by cholera toxin (CT) but the presence of a PDE inhibitor was required for such enhancement to become evident. Pretreatment of macrophages with cytochalasin B, an agent interfering with microfilament function, had no effect on the responsiveness of the cells to AC stimulators. The microtubule stabilizer, deuterium oxide (D2O) partially reversed the colchicine effect. Microtubule disrupting drugs did not block the release of cAMP from the cells into the surrounding medium. Macrophages incubated as monolayers or in suspension showed the same degree of increased responsiveness to stimulators after preexposure to colchicine. Preincubation with the ionophore A23187, which elevates the intracellular concentration of Ca2+, also enhanced the stimulation of AC by PGE1 and IP. Microtubule disrupting agents did not potentiate AC activity in broken cell preparations, whether added to the intact cells before disruption or directly to the enzyme assay mixture, nor did they affect PDE activity of macrophage sonicates. Moderate enhancement of PGE1-induced cAMP formation was also seen in colchicine- and vinblastine-treated lymphocytes. It was concluded that microtubules control the activity of AC by restricting the mobility of membrane receptors. Disruption of microtubules by drugs results in the removal of such restraints and an augmented chance of productive interactions between receptors and catalytic units of AC.
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PMID:Enhancement of macrophage adenylate cyclase by microtubule disrupting drugs. 4 91

Cyclic AMP has been implicated in the regulation of the immunologic release of histamine from lung and other tissues and cell types. The mechanism whereby intracellular levels of cAMP are altered during mediator release was investigated. Measurements of histamine, adenylate cyclase, and cAMP phosphodiesterase activities were made in actively and passively sensitized guinea pig lung after challenge with antigen. A transient decrease in basal adenylate cyclase activity occurred which returned to control levels after histamine release. There was no change in cAMP phosphodiesterase activity determined at substrate concentrations of 1 mM and 0.01 mM. The adenylate cyclase response did not occur under the following conditions: 1) incubation of nonsensitized lung with antigen, 2) incubation of sensitized lung with antigen in the absence of extracellular calcium, and 3) incubation of nonsensitized lung with compound 48/80. These observations indicate 1) the adenylate cyclase response and the immunologic release of histamine are intimately related, and 2) the reduction in intracellular levels of cAMP which have been reported to occur during immunologic histamine release are mediated via adenylate cyclase.
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PMID:Reduction in basal adenylate cyclase activity during the immunologic release of histamine from guinea pig lung. 6 29


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