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)

Activity, ratio and summary content of cyclic AMP enzymes, adenylate cyclase and phosphodiesterase varied depending on growth conditions of phototrophic bacteria (Rhodospirillum rubrum and Rhodopseudomonas palustris). It suggests, that membrane-bound and soluble enzymes carry different functions. The increase of adenylate cyclase under chaning growth conditions was usually accompanied by the increase of phosphodiesterase. Sharp increase of both enzymes activity was observed when bacteria were growth in aerobic conditions. The activity of both enzymes in chromatophores was 2.8-fold higher when bacteria were grown in the light in anaerobic conditions, than in chromatophores of bacteria grown under stationary aerobic conditions in the light. It is suggested that 3':5' AMP can participate in autotrophic carbon assimilation or in the synthesis of pigments and other components of bacterial photosynthetizing apparatus. Substitution of NH4+ into NO3- and glutamate under the growing of R. rubrum in anaerobic conditions in the light resulted in the increase of the enzymes activities, which is the evidence of possible role of 3':5' AMP in mineral nitrogen uptake and nitrogen fixation. Glutamate concentration of 4 g/l stimulated the enzymes both in vivo and in vitro. The data obtained suggest that 3':5' AMP can carry multiple functions, participating in regulation of a number of metabolic processes in photorophic bacteria.
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PMID:[Effect of growth conditions on the activity of the enzymes of cyclic 3':5'-AMP synthesis and decay in phototrophic bacteria]. 20 63

In Triton X-100-skinned trachealis muscle, neither papaverine nor AH 21-132 modified responses to Ca2+. The (-)-enantiomer of AH 21-132 was more potent than the (+)-enantiomer both in relaxing intact trachealis muscle and in inhibiting tracheal cAMP phosphodiesterase (PDE). AH 21-132 (0.6 microM) potentiated forskolin in causing tracheal relaxation but did not potentiate isoprenaline, cromakalim or sodium nitrate. AH 21-132 (2 microM) potentiated all four agents in relaxing the trachea. AH 21-132 (1 microM) potentiated forskolin in increasing tissue cAMP content and, in higher concentration, itself increased tissue cAMP. Electrical effects of AH 21-132 included suppression of spontaneous slow waves and cellular hyperpolarisation. It is concluded that AH 21-132 lacks a direct depressant effect on the intracellular contractile machinery. The weight of evidence suggests that AH 21-132-induced relaxation results from inhibition of cAMP-PDE. However, in common with other PDE inhibitors. AH 21-132 increases tissue cAMP content only at concentration greater than that required to cause full relaxation.
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PMID:Biochemical and electrical aspects of the tracheal relaxant action of AH 21-132. 164 18

Recent studies have more clearly defined the role of drug therapy in patients with chronic congestive heart failure (CHF). Treatment of patients with asymptomatic left ventricular dysfunction (New York Heart Association [NYHA] class I) cannot be recommended at this time. The benefit of prophylactic treatment with angiotensin-converting enzyme inhibitors (ACEIs) or vasodilators in patients at high risk for developing symptomatic CHF is currently being evaluated. Treatment of patients with symptomatic CHF (NYHA class II-IV) should be initiated with a combination of a diuretic, digoxin, and an ACEI. This combination has been shown to reduce the mortality rate in patients with NYHA class II-IV CHF. Patients who remain symptomatic despite treatment with this combination may benefit from the addition of the direct-acting, nonspecific vasodilators--hydralazine and a nitrate. The addition of the nonspecific vasodilators to an ACEI has not been tested in controlled trials. In patients who remain symptomatic despite treatment with diuretics, digoxin, ACEIs, and nonspecific vasodilators, treatment options are not clear. The use of beta-agonists, phosphodiesterase inhibitors, and intermittent fixed-dose, fixed-interval dobutamine should be avoided as these agents are associated with a high mortality rate. Heart transplantation should be considered early in the course of CHF to allow for preservation of other vital organ systems. Unfortunately, heart transplantation is available to only a very small minority of potential transplant candidates.
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PMID:Changing strategies in the management of chronic congestive heart failure. 166 16

Low concentrations of sodium nitroprusside (0.2 and 1 microM) relaxed carbachol-induced tone of the rat anococcygeus but did not affect the content of either cGMP or cAMP; higher concentrations (10,100 and 1000 microM) produced greater relaxation (greater than 60%) and a rise in cGMP but not cAMP. In the presence of the cGMP-phosphodiesterase inhibitor M&B 22948 (10 microM), 1 microM sodium nitroprusside produced greater relaxation and a selective increase in cGMP. Forskolin (0.5-250 microM) caused relaxation and a selective increase in cAMP; the concentration-response relationships of the two effects were similar. Non-adrenergic, non-cholinergic (NANC) field stimulation (10 Hz; 20 s trains) reduced tone by 52% but had no effect on cyclic nucleotide content; in the presence of 10 microM M&B 22948 or 1 microM sodium nitroprusside, NANC stimulation produced a greater degree of relaxation and increased cGMP but not cAMP content. The results show that NANC stimulation acts like sodium nitroprusside, causing a selective increase in cGMP, and this supports the proposal that NANC transmission in the rat anococcygeus involves an endogenous nitrate; the possibility that multiple pools of cGMP exist in the anococcygeus is discussed.
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PMID:Cyclic nucleotide content of the rat anococcygeus during relaxations induced by drugs or by non-adrenergic, non-cholinergic field stimulation. 167 36

Glutamine synthetase from Synechocystis sp. strain PCC 6803 is inactivated by ammonium addition to cells growing with nitrate as the nitrogen source. The enzyme can be reactivated in vitro by different methods such as alkaline phosphatase treatment, but not phosphodiesterase, by raising the pH of the crude extract to values higher than 8, by increasing the ionic strength of the cell-free extract, or by preincubation with organic solvents, such as 2-propanol and ethanol. These results suggest that the loss of glutamine synthetase activity promoted by ammonium involves the non-covalent binding of a phosphorylated compound to the enzyme and support previous results that rule out the existence of an adenylylation/deadenylylation system functioning in the regulation of cyanobacterial glutamine synthetase.
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PMID:In vitro reactivation of in vivo ammonium-inactivated glutamine synthetase from Synechocystis sp. PCC 6803. 168 95

We used ultrastructural cytochemistry to localize adenylate cyclase activity in the three evolutive forms of Trypanosoma cruzi. We detected the enzyme by using adenylimidodiphosphate as substrate, prostaglandin E1 as enzyme stimulator, theophylline as inhibitor of adenosine 3'-5'-monophosphate phosphodiesterase, and either cerium chloride or lead nitrate as capture agent. Deposition of imidodiphosphate was stronger in trypomastigotes than in amastigotes and epimastigotes. Differences in the reaction product levels between the nonproliferative form and both proliferative ones are in accordance with our previous work that showed the involvement of adenylate cyclase on the control of T. cruzi's cycle.
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PMID:Cytochemical localization of adenylate cyclase in the three developmental forms of Trypanosoma cruzi. 181 3

The relaxant effects of nitroglycerin (NTG) and SIN1 on human vena saphena magna were studied in vitro. Nitrate tolerance was produced after incubation of the preparation with nitroglycerin (NTG 10 microM for 10 minutes). Vessels precontracted by serotonin (0.25 microM) and made tolerant to NTG exhibited a slight but significant shift (p less than 0.01) to the right of the dose-response curve to SIN1 (EC50 increased from 1.12 +/- 0.21 microM to 2.74 +/- 0.32 microM). The maximal relaxation was unaltered. On the contrary, there was a marked attenuation of the maximal relaxation to NTG in the nitrate-tolerant preparation (maximal relaxation decreased from 73 +/- 2% to 35 +/- 1%). Dipyridamole, a phosphodiesterase (PDe) inhibitor, significantly potentiated the responses to SIN1 on control rings (EC50 = 57.1 +/- 1.8 nM), and on NTG-tolerant rings it reversed the responsiveness to SIN1 (EC50 = 88.9 +/- 9.2 nM), which suggests that nitrate tolerance may be partially due to an increase in PDe activity. In conclusion we have demonstrated a slight cross-tolerance between SIN1 and NTG on human vena saphena magna. Nevertheless, after induction of in vitro NTG tolerance, the attenuation of responses to SIN1 is much less pronounced that the alteration of NTG relaxations.
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PMID:Effect of nitrate tolerance and dipyridamole on the response to SIN1 in the human isolated saphenous vein. 190 34

Nitrate tolerance is defined as an attenuation or even loss of hemodynamic and anti-ischemic effects during continuous nitrate medication. The blunted response may be due to the development of pseudotolerance and true pharmacologic tolerance. Pseudotolerance is the result of volume and salt retention, as well as the stimulation of counter-regulatory mechanisms which may alter the baseline hemodynamics of a patient during nitrate therapy. Far less important are changes in nitrate pharmacokinetics. True pharmacological tolerance may also be of practical importance. Diminished uptake of nitrates into the vascular smooth muscle cell, a decrease in intracellular SH groups, inhibition of the guanylate-cyclase, and stimulation of a specific phosphodiesterase may result in a decrease of cyclic GMP formation and hence to a decrease in nitrate induced vasodilatation. Tolerance development may be prevented by intermittent nitrate administration providing intervals with low plasma and tissue nitrate levels. In consequence, nitrates should be used predominantly for treatment of ischemic episodes, but 24-hour anti-ischemic action for the prevention of ischemia can be better achieved by treatment with a beta-blocker and/or a calcium antagonist. Nitrates should be added in times of maximum susceptibility to ischemia, while allowing nitrate levels to fall at other times.
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PMID:[Nitrate tolerance]. 290 73

Tolerance to nitrate vasodilators appears to be a general phenomenon that encompasses all known drugs belonging to this group, with the possible exception of molsidomine, for which tolerance has not yet been unambiguously proven. The mechanism behind tolerance development is still obscure, although decreased distribution of drug to the target tissue (i.e. the vascular wall) may be important. In addition, the production of cyclic guanosine-3',5'-monophosphate (cGMP) [the alleged mediator of nitrate-induced vascular smooth muscle relaxation] is reduced in tolerant tissue, while its degradation is increased. These changes could be due to a direct effect on the enzymes involved in the formation and degradation of cGMP in the cell, i.e. guanylate cyclase and phosphodiesterase, respectively. Furthermore, there is some evidence that the degradation of organic nitroesters in the vascular wall is reduced in tolerant tissue. This could result in a reduced production of unstable chemical intermediates (e.g. nitrosothiols), which have been suggested to act as mediators of guanylate cyclase.
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PMID:Nitrate tolerance from a biochemical point of view. 304 Mar 74

Annual mortality from congestive heart failure ranges from 15% to 60%, depending on the severity of the left ventricular damage and underlying disease. Most controlled trials have been too small to detect any beneficial effect on survival from the newer vasodilator and inotropic drugs. However, the results of two recent studies strongly suggest that some vasodilator drugs improve prognosis. In one study, a hydralazine-nitrate combination reduced 2-year mortality by 34%, while in another study, enalapril, in addition to diuretics, digitalis, and directly acting vasodilators, reduced 1-year mortality by 31%. Thus far no large studies have been published with the new phosphodiesterase-inhibiting agents. Although preliminary reports of large-scale trials did not demonstrate changes in survival rate, they have been shown to improve well-being in class III-IV congestive heart failure patients.
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PMID:Therapeutic advances in heart failure. 315 50


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