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 involvement of tissue cAMP in the vasodilating action of parathyroid hormone (PTH) was investigated. The bovine active fragment bPTH-(1-34) was used in all studies. In anesthetized dogs, theophylline, a phosphodiesterase inhibitor, potentiated the hypotensive action of bPTH-(1-34) at the dose of 1 microgram/kg. The potentiation was related to the dose of theophylline infused. In an in vitro rat tail artery helical strip assay, dibutyryl cAMP produced dose-related relaxation in arginine vasopressin (AVP) constricted blood vessels. bPTH-(1-34) also produced dose-related relaxation in the tail artery constricted by AVP. In the presence of isobutylmethylxanthine, another phosphodiesterase inhibitor, the bPTH-(1-34) dose--response curve was shifted to the left, indicating potentiation. Imidazole, which has phosphodiesterase stimulating activity, significantly decreased the in vitro vasorelaxing effect of bPTH-(1-34). In addition, bPTH-(1-34) increased significantly the rat tail artery cAMP content. b-PTH-(1-34) oxidized with hydrogen peroxide lost its vasorelaxing activity and was also ineffective in increasing the tail artery cAMP content. All these data strongly suggest that cAMP may be involved in eliciting the vasorelaxing action of bPTH-(1-34).
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PMID:Cyclic AMP and the vascular action of parathyroid hormone. 243 93

The role of cyclic AMP in cell proliferation and division has been the subject of study by a number of investigators in the past 30 years, but the argument of whether cyclic AMP is a negative or a positive regulator has not been settled. We studied the effect of cyclic AMP on proliferation of normal and postpneumonectomized lung tissues in young adult rats by measuring the incorporation of tritiated thymidine into lung DNA in organ culture. In normal lung tissues the incorporation of [3H]thymidine was increased by exogenous dibutyryl cyclic AMP, or by isoproterenol or forskolin to stimulate adenylate cyclase, or by caffeine, which inhibits cAMP phosphodiesterase. The effect of isoproterenol, but not forskolin, was abolished by the beta-adrenergic blocking agent propranolol. The effect of caffeine on [3H]thymidine incorporation was further enhanced in normal lung tissues in the presence of dibutyryl cyclic AMP and in postpneumonectomized lung tissues. Imidazole, a cAMP phosphodiesterase stimulator, also increased [3H]thymidine incorporation in culture, but the effect was not magnified in the presence of exogenous dibutyryl cyclic AMP, nor in postpneumonectomized lung tissues. The data suggest that cyclic AMP acts as a positive regulator in proliferation of lung tissues.
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PMID:Role of cyclic AMP in proliferation of lung tissue in organ culture. 254 31

Prostaglandin E2 (PGE2) induced a dose-dependent increase in tone of the circular muscles of guinea pig ileum in vitro. These actions of PGE2 were deleted in the cold-stored preparations and blocked by tetrodotoxin. Atropine reduced the effects of PGE2 and physostigmine potentiated the PGE2-induced contractions. The release of acetylcholine (ACh) by PGE2 was responsible for initiating this contraction. The effect of PGE2 was compared with that of an electrical stimulation which also initiated a non-receptor-mediated release of ACh. Hexamethonium abolished the effect of PGE2 but did not influence the actions of the electrical stimulations. Synaptosomal fractions of the circular muscles were prepared to study the release of [14C]ACh. However, PGE2 failed to evoke a marked increase in the efflux of radioactivity, even at the maximal concentration. Damage and/or removal of the myenteric plexus may be responsible for this result because electrical stimulations that exert a powerful spasmogenic effect on longitudinal muscles also induced an insensitive response. Alloxan and ethacrynic acid, inhibitors of adenylate cyclase, reduced the activity of PGE2 at a concentration insufficient to modify either the actions of ACh or the electrical stimulations. 3-Isobutyl-1-methylxanthine (IBMX) potentiated the responses to PGE2 at a dose sufficient to block the activity of phosphodiesterase (PDE). Imidazole, a stimulator of PDE, decreased the actions of PGE2 in a dose-dependent manner. IBMX, like imidazole, failed to modify the activities of both ACh and the electrical stimulations. These results indicate that PGE2 may function as a releaser of ACh in a cyclic AMP-dependent manner in the circular muscles of guinea pig ileum.
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PMID:Prostaglandin E2 induced the cyclic AMP-dependent release of acetylcholine in circular muscles of the isolated guinea pig ileum. 283 81

Imidazole, a phosphodiesterase stimulator potentiated the responses of rat uterus to 5-HT, without increasing the maximal response. Aminophylline, papaverine and diazoxide significantly inhibited the responses to 5-HT including the maximal response. Imidazole did not affect the inhibitory effect of aminophylline, papaverine and diazoxide. The effect of imidazole on myometrium may be due to its direct effect on membrane permeability resulting in an increased influx of calcium. Phosphodiesterase stimulation if at all seems to play only a minor role.
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PMID:Modulation of 5-hydroxytryptamine-evoked responses of the isolated rat uterus by imidazole, a phosphodiesterase stimulator. 299 37

Preliminary studies (Lineweaver-Burk, Ca2+ calmodulin sensitivity) suggest that oral mucosa contains at least two cyclic AMP phosphodiesterases, one a high affinity (low Km) enzyme and the other a low affinity (high Km) enzyme. Analysis of the distribution of both enzymatic forms during oral mucosal regeneration revealed that the low Km, and high Km cAMP phosphodiesterase activities were significantly elevated prior to the first wave of cAMP accumulation and during the second cAMP wave. Although the cAMP peaks declined between 20-24 h, both cAMP phosphodiesterases remained significantly elevated at the wound site. The apparent Km of the low Km form increased from 5.3 to 7.5 microM, while that of the high Km form remained essentially unaltered 20 h after wounding. The low Km, and high Km cAMP phosphodiesterase activities in normal rat oral mucosa were not affected by epinephrine or insulin; were slightly inhibited by glucagon, and significantly inhibited by methylprednisolone. Imidazole and histamine activated both forms and theophylline was inhibitory to the enzyme. The high Km cAMP phosphodiesterase was sensitive, and the low Km form insensitive to Ca2+ calmodulin stimulation.
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PMID:Changes in cAMP phosphodiesterase activity during oral mucosal regeneration. 300 61

In isolated snail brain, the role was studied of cyclic adenosine monophosphate (cAMP) in providing plastic properties of electro-excitable neuronal membranes of two types, habituating and non-habituating to rhythmic intracellular stimulation with depolarizing electric pulses. It has been shown that at high level of cAMP in the cell maintained with administration of dibutyryl-cAMP and (or) blockaders of phosphodiesterase in incubation medium, habituating cells lose their ability of habituation to stimulation. There is also no habituation in the presence of serotonin: serotonin effect is removed by imidazol, activator of phosphodiesterase. Imidazol promotes the development of habituation of cells, initially non-habituating to stimulation. Data are obtained on connection of Ca2+ effects and cAMP metabolism in habituating cells. On the basis of the obtained data it is suggested that the cyclase system controls plastic properties of neurones of both types, and reduction of cAMP content in the cell apparently mediates the above mentioned Ca-K-mechanism of habituation.
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PMID:[Role of cAMP in providing for the plastic properties of the electro-excitable membrane of neurons]. 303 35

We studied the effect of the ionophere A 23187 and of phosphodiesterase inhibitors and activators (Theophylline, Pentoxiphylline and Imidazol) on insulin secretion and on the pool of free tubulin in rat pancreas in the presence of somatostatin and diazoxide. The results suggest that: 1. The inhibitory effect of somatostatin on insulin secretion does not seem to be related mainly to an inhibition of cAMP production. The decrease in calcium translocation induced by somatostatin could inhibit the cAMP participation in the mechanism of hormonal secretion. 2. Somatostatin seems to inhibit the movement of calcium towards the cytoplasm from outside and from within the cell. Diazoxide seems to inhibit only the entrance of calcium from outside the cell but does not seem to inhibit the entrance determined by theophylline and pentoxiphylline from intracellular compartments. 3. Arginine glucose stimulation in the presence of A 23187-induced calcium translocation is able to determine insulin secretion although cAMP degradation is increased by imidazol. 4. Somatostatin and diazoxide inhibit pancreatic tubulin polimerization; however, the effect seem to be indirect and related to the inhibition of calcium translocation determined by both substances.
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PMID:A comparative study of two insulin secretion inhibitors: somatostatin and diazoxide. 612 27

Imidazole, at concentrations between 10(-3) and 10(-2) M, exerts a profound stimulatory effect on rabbit uterine strips obtained during pregnancy and studied isometrically in vitro. The action is not duplicated by N-alkylimidazoles which have greater potency as inhibitors of thromboxane synthetase but the effect of imidazole was antagonized by isoproterenol or theophylline. Biochemical analysis indicated that imidazole at concentrations greater than 5 x 10(-4) M stimulated both high and low affinity forms of cyclic AMP phosphodiesterase. The uterus of pregnant rabbits is profoundly refractory to any kind of pharmacological stimulation and the effects of imidazole, acting to stimulate phosphodiesterase, suggest that the integrity of the adenyl cyclase-cyclic AMP-protein kinase system is a necessary requirement for this organ to remain quiescent during pregnancy.
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PMID:Enhanced excitability of the uterus of the pregnant rabbit by imidazole stimulation of cyclic AMP phosphodiesterase. 625 37

We have measured the changes in C2 production and in cyclic nucleotide levels in mononuclear leucocytes cultured in the presence of agents which change intracellular cAMP. Adenylcyclase activators, cholera toxin and phosphodiesterase inhibitors increased cAMP levels and reduced C2 production. Imidazole, hydrocortisone and prostaglandin synthetase inhibitors reduced cAMP and increased C2 synthesis. The level of cAMP after 2 hr incubation showed an inverse correlation with C2 levels in the culture supernatants. When histamine, which increases cAMP and reduces C2 production, and imidazole, which reduces cAMP and increases C2 synthesis, were added together, levels of cAMP and C2 did not differ significantly from those found in control cultures. On the basis of these observations we have concluded that changes in monocyte cAMP alter the production of C2.
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PMID:Control of monocyte C2 production by cyclic AMP. 630 65

Imidazole (3.67 x 10(-3) M) and sodium bicarbonate (1.78 x 10(-2) M) failed to alter acetylcholine evoked responses in isolated rat uterus but they produced a significant shift of the log dose-response curve of oxytocin to the left. This potentiating effect was reversible. Addition of imidazole increased the pH of de Jalon solution from 7.2 to 8.5. Sodium dihydrogen orthophosphate (3.3 x 10(-3) M) prevented the change of pH due to the addition of imidazole and at the same time the potentiating effect of imidazole was inhibited. The present study strongly suggests that the potentiation of oxytocin-evoked responses by imidazole is due to the change in pH of de Jalon solution towards more alkaline range and it may not be due to stimulation of phosphodiesterase activity of rat uterus.
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PMID:Effect of imidazole on oxytocin and acetylcholine induced responses in isolated rat uterus: with observations on its mechanism of action. 743 34


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