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 mechanism of action of aminophylline in prolonging seizures was tested in amygdala-kindled rats. Aminophylline prolonged the afterdischarge duration of kindled seizures. This seizure-prolonging action of aminophylline was strongly antagonized by the adenosine A1 agonist cyclohexyladenosine and partially antagonized by the benzodiazepine partial agonist RO 15-1788. However, the specific benzodiazepine antagonist CGS 8216 did not affect the seizure-prolonging action of aminophylline. Also, the potent anticonvulsant effect of diazepam on kindled seizures, which was completely antagonized by CGS 8216, was unaffected by aminophylline. Furthermore, a range of benzodiazepine inverse agonists, GABA antagonists, phosphodiesterase inhibitors and xanthines did not prolong afterdischarge durations. These results demonstrate that the seizure-prolonging action of aminophylline is due to block of A1 adenosine receptors since it is prevented by adenosine A1 agonists.
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PMID:Adenosine receptor antagonism accounts for the seizure-prolonging effects of aminophylline. 221 1

Two forms of cAMP phosphodiesterase were isolated from lymphocytes by using centrifugation in sucrose density gradient. The activities of both forms do not differ in healthy persons and in patients with bronchial asthma during asphyxia-free period. During the attack the activity of the high molecular form of the enzyme increases. Euphylline exerts the inhibitory effect on the activity and consequently on the general activity of the enzyme.
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PMID:[Characteristics of the action of euphylline and the activity of forms of cAMP phosphodiesterase in lymphocytes of patients with bronchial asthma]. 255 34

In chronic pancreatitis with moderate derangements of carbohydrate tolerance (detected by the double glucose test), the basal concentrations of insulin and C-peptide in blood are normal whereas in patients with secondary diabetes mellitus are lowered. Glucagonemia is increased in patients of both groups. Euphylline (applied as an inhibitor of nucleotide phosphodiesterase), calcium gluconate and the adrenomimetic drug isadrin consistently increased insulinemia and the blood level of C-peptide in patients with chronic pancreatitis both with moderate and appreciable derangements of glucose tolerance. In patients with secondary diabetes that developed in the presence of pancreatitis, these drugs did not influence glucagonemia. The clinical prospects of the making use of the stimulating action of euphylline, calcium gluconate and isadrin on the function of beta-cells of the pancreas in chronic pancreatitis patients are under discussion.
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PMID:[The effect of pharmacological agents on pancreatic incretory activity in patients with chronic pancreatitis]. 269 52

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

The biochemical mechanisms by which nitroso-vasodilators cause smooth muscle relaxation remain controversial. One theory states that the effects of nitroso-vasodilators are mediated by increased intracellular levels of cyclic GMP due to activation of guanylate cyclase. To test this hypothesis, the authors examined the effects of sodium nitroprusside (SNP) in anesthetized dogs with an without pretreatment with the phosphodiesterase inhibitor aminophylline. Aminophylline pretreatment resulted in a 2.8-fold potentiation of the hypotensive effects of a continuous infusion of SNP. Potentiation also was seen for the effects of SNP on stroke volume, heart rate, and plasma cyclic GMP levels. These results support the hypothesis that nitroso-vasodilators exert their effects via guanylate cyclase activation. The authors advise caution when vasodilator therapy with agents such as SNP, nitroglycerin, or hydralazine is instituted in patients receiving aminophylline and when aminophylline is either instituted or discontinued in patients on vasodilator therapy.
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PMID:Aminophylline potentiates sodium nitroprusside-induced hypotension in the dog. 609 2

The effect of cAMP analogues on phosphatidylcholine formation via the CDP-choline pathway was investigated in cultured monolayers of rat hepatocytes. Treatment with chlorophenylthio-cAMP or the cAMP phosphodiesterase inhibitor, aminophylline, reduced the total uptake of [methyl-3H]choline by 32 and 26% (p less than 0.01), respectively. Chlorophenylthio-cAMP inhibited the incorporation of [methyl-3H]choline into phosphatidylcholine by 2.5-fold (p less than 0.001) and reduced the rate of phosphatidylcholine biosynthesis by approximately 40%. Aminophylline, 8-bromoadenosine 3':5'-monophosphate and N6,O2'-dibutyryladenosine 3':5'-monophosphate also inhibited [methyl-3H]choline incorporation into phosphatidylcholine. Although choline kinase and phosphocholinetransferase activities were stimulated by chlorophenylthio-cAMP treatment, CTP: phosphocholine cytidylyltransferase activity was reduced 46% (p less than 0.01). The results indicate that cytidylyltransferase may be phosphorylated and inhibited by cAMP-dependent protein kinases.
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PMID:cAMP analogues inhibit phosphatidylcholine biosynthesis in cultured rat hepatocytes. 616 76

We have investigated the role in macrophage lysosomal enzyme release of arachidonate metabolites, extracellular divalent cations and cyclic AMP (cAMP) which modulate secretion in other cell types. Lysosomal enzyme secretion induced by zymosan was accompanied by release of malondialdehyde (MDA), which is derived from arachidonic acid via prostaglandin synthase. Blockade of MDA formation, by aspirin or indomethacin, was associated with only a small inhibitory effect on lysosomal enzyme release by zymosan: arachidonate metabolites thus play only a minor role in mediating macrophage lysosomal enzyme release. Zymosan-induced secretion of lysosomal enzymes from macrophages did not require extracellular magnesium or calcium although release was enhanced by magnesium and inhibited by calcium. These effects may be related to an influence of the ions on phagocytosis. Elevation of intracellular divalent cation concentrations, by ionophore A23187, induced release of lysosomal enzymes but this was a result of cell lysis. Adenylate cyclase stimulants and dibutyryl cAMP produced slight inhibition of zymosan-induced lysosomal enzyme release. Aminophylline and papaverine caused more marked inhibition but their effects may be due to actions independent of phosphodiesterase inhibition. Our data indicate that arachidonate metabolites and cAMP do not play a major role in regulating zymosan-induced enzyme release from macrophages. Extracellular calcium and magnesium may modulate secretion but the role of intracellular divalent cations remains to be established. We conclude that macrophage lysosomal enzyme secretion is controlled by regulatory mechanisms different from those which control similar degranulation processes in other cell types.
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PMID:Regulation of macrophage lysosomal enzyme secretion: role of arachidonate metabolites, divalent cations and cyclic AMP. 625

There are conflicting results regarding the impact of cyclic AMP on pancreatic glucagon release. The effect of aminophylline, a phosphodiesterase inhibitor, on glucagon secretion was studied in four non-obese, non-diabetic, healthy young male volunteers. The subjects received separate infusions of: 1) aminophylline; 2) aminophylline and propranolol; 3) arginine; 4) aminophylline and arginine; 5) insulin; 6) aminophylline and insulin; and 7) aminophylline and isoproterenol. Aminophylline not only failed to alter glucagon levels but also did not affect the glucagon responses observed after arginine and insulin-induced hypoglycemia. The concurrent infusion of isoproterenol and aminophylline also failed to cause a glucagon response. Although glucagon release has been evoked by cyclic AMP in some in vitro system, administration of aminophylline to human subjects does not enhance secretion. These results indirectly suggest that cyclic AMP is of little importance in the control of glucagon secretion in man, though the effects of aminophylline at the cellular level may be complex.
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PMID:The failure of aminophylline to modulate glucagon release in man. 628 47

The changes in airway caliber and plasma cyclic-AMP levels after intravenously administered aminophylline, and the effect of DL- and D-propranolol on these responses have been investigated in a double-blind manner in normal subjects. Aminophylline 5.6 mg/kg was given intravenously over a 10-min period and the airway response was measured as change in specific airway conductance (delta SGaw) in the body plethysmograph. In the initial study in 6 subjects, orally administered placebo or propranolol was followed 2 h later by intravenously administered aminophylline. Neither placebo nor propranolol alone caused any change in SGaw at 2 h. After placebo, intravenously injected aminophylline produced a 30% increase in SGaw, reaching a peak 5 min after injection. This response was equivalent to 77% of the maximal response to 400 micrograms inhaled albuterol in the same subjects. After propranolol, the airway response to aminophylline was attenuated, with a 53% reduction in delta SGaw at the time of peak response. In a further study on 6 subjects, intravenously given aminophylline produced a 25% increase in SGaw and a 51% increase in plasma cyclic-AMP levels after placebo tablets. Pretreatment with 40 and 80 mg DL-propranolol caused a dose-dependent reduction of both the airway and plasma cyclic-AMP response to aminophylline. The airway response to aminophylline was not attenuated by D-propranolol so the effect of DL-propranolol is thought to be due to beta-adrenoceptor blockade. The absence of any detectable change in SGaw after DL-propranolol suggests there is little resting sympathetic tone to the airways in normal subjects. In the absence of sympathetic stimulation, the rapid response to aminophylline is unlikely to be due to phosphodiesterase inhibition. The attenuation of the airway and cyclic-AMP response by propranolol suggests that part of the action of aminophylline may be due to beta-agonist activity.
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PMID:Action of intravenously administered aminophylline on normal airways. 630 66

The antithrombotic efficacy of prostacyclin (PGI2) when administered in conjunction with the phosphodiesterase inhibitor aminophylline was evaluated in a canine model in which coronary artery thrombosis was induced by electrical stimulation of the intimal surface of the left circumflex (LCX) coronary artery. Infusions of PGI2 (25 or 50 ng/kg/min) into the left atrial appendage and aminophylline (20 micrograms/kg/min) or ethylene diamine into the left jugular vein were initiated 10 min before the start of LCX coronary artery stimulation and continued for the 6-hr stimulation period. Every animal in the control (Tris buffer plus ethylene diamine, n = 7), PGI2 (25 ng/kg/min) only (n = 6) and aminophylline only (n = 7) groups developed completely occlusive coronary artery thrombi. In contrast, none of the animals receiving PGI2 (25 ng/kg/min) plus aminophylline or PGI2 (50 ng/kg/min) plus aminophylline underwent occlusive thrombus formation. The average thrombus mass developed in response to intimal injury of the LCX coronary artery was 57 +/- 14 mg (X +/- S.E.M.) in the control group. Aminophylline administration in conjunction with PGI2 infusion at doses of 25 and 50 ng/kg/min significantly reduced thrombus mass to 11 +/- 2 and 10 +/- 1 mg, respectively (P less than .05). PGI2 (25 ng/kg/min) plus aminophylline reduced mean arterial pressure by 12% from 116 +/- 5 to 102 +/- 4 mm Hg. These data demonstrate that the combined administration of aminophylline with low-dose PGI2 provides antithrombotic efficacy while minimizing the detrimental hemodynamic effects of large-dose PGI2 administration.
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PMID:Potentiation of the antithrombotic effect of prostacyclin by simultaneous administration of aminophylline in a canine model of coronary artery thrombosis. 631 94


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