Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Imidazole administered intraperitoneally to albino rabbits at a dose of 250 mg. per kilogram inhibited the rise of aqueous humor protein concentration by approximately 50 per cent 30 minutes after paracentesis. Systemic imidazole administered daily to albino rabbits injected with intravitreal Shigella endotoxin decreased the conjunctival and iris hyperemia and reduced the anterior chamber cell and flare and the haziness of the optical media. Systemically administered imidazole had no effect on the aqueous humor concentrations of c-AMP or c-GMP in the rabbit. In vitro studies of rabbit ciliary body-iris phosphodiesterase activity indicated no effect of imidazole at a concentration of 10(-3) molar.
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PMID:The ocular anti-inflammatory action of imidazole. 18 77

Following the addition of carbachol or acetylcholine to microsomal fractions isolated from rabbit colon which were preloaded with Ca, the ions were rapidly released. In the 35-45% fraction Ca was completely released within 10 min., but in the 35% fraction only 30% was released. Carbachol reduced the adenylate cyclase activity of the 35-45% fraction. Both these effects were blocked by atropine. Exogenous cyclic AMP completely inhibited the Ca-releasing action of carbachol in the 35% fraction and markedly reduced it in the 35-45% fraction. Imidazole released Ca from the 35-45% fraction and stimulated its phosphodiesterase activity. It is suggested that the microsomal fractions are parts of a Ca-sequestering system in smooth muscle which are able to bind Ca and which on the addition of some contracting drugs release the ions and thereby activate the contractile system. The release of Ca may partly at least be due to a reduction of the adenylate cyclase activity, although other mechanisms must also be considered.
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PMID:Effects of cholinergic drugs and imidazole on Ca release and cyclic AMP formation in microsomal fractions from rabbit colon. 19 Aug 60

A survival period of irradiated rat thymocytes was studied after administration of several possible modifiers of intracellular 3',5'-cyclo AMP. Theophylline, which inhibits 3',5'-cyclo AMP phosphodiesterase, adrenaline, ATP and adenosine possessed a radioprotective effect if they were added before the irradiation or just immediately after it. Imidazole activated 3',5'-cyclo AMP phosphodiesterase and, being added within the above-mentioned periods, it shortened the survival period at the irradiated cells. When theophylline and imidazole were added within 30 min after the irradiation, their effect was completely altered: imidazole increased but theophylline decreased the survival period of the irradiated cells. 3',5'-cyclo AMP and N6-2'-0-dibutyryl-3',5'-cyclo AMP did not affect the viability of thymocytes after the irradiation.
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PMID:[Study of the role of endogenous 3',5'-cyclic AMP in the radioresistance of the cell]. 19 14

The influence of phosphodiesterase inhibitors, imidazole and dBcAMP on the action of histamine on peak tension, on rate of tension development and rate of relaxation of ventricular muscle of guinea pig's heart was investigated. It was found that theophylline plus dBcAMP enhanced the peak tension, (dF/dt)max and the rate of relaxation and increased the relaxing action of histamine. Imidazole, an activator of phosphodiesterase, also potentiated the action of histamine on peak tension, (dF/dt)max and rate of relaxation. Caffeine, a well-known inhibitor of phosphodiesterase, suppressed the relaxing action of histamine and epinephrine. These discrepant results could be explained by assuming the possibility that these drugs have effects other than those involving inhibition and activation of phosphodiesterase.
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PMID:Effect of phosphodiesterase inhibitors and dBcAMP on the inotropic and relaxing actions of histamine in cardiac muscle. 19 18

1 Nicotinic acid and alloxanate inhibited water and electrolyte secretion in a dose-dependent fashion when added to the perfusate of the isolated saline-perfused pancreas of the cat stimulated by a supramaximal dose of secretin.2 There were no changes in the concentration of sodium or potassium secreted into the juice, but the anions exhibited changes which were related to flow rate. As the flow rate declined the chloride concentration increased with a reciprocal decrease in bicarbonate concentration.3 Nicotinic acid and alloxanate inhibited enzyme secretion stimulated by carbachol.4 Imidazole inhibited pancreatic electrolyte secretion, but stimulated amylase secretion. Atropine (0.14 muM) reduced the secretion of amylase but did not abolish the effect.5 Adenylate cyclase prepared from cat pancreas, was stimulated by the octapeptide of cholecystokinin-pancreozymin, secretin and sodium fluoride.6 Alloxanate strongly inhibited both basal and hormone-stimulated adenylate cyclase activity. Nicotinic acid and imidazole stimulated basal adenylate cyclase activity but had little effect on secretin-stimulated activity.7 Alloxanate, nicotinic acid and imidazole were all without effect on phosphodiesterase when tested in the presence of micromolar concentrations of adenosine 3',5'-monophosphate (cyclic AMP). At higher cyclic AMP concentrations (2 mM) alloxanate and nicotinic acid were without effect, whereas imidazole had a slight stimulatory effect at 10 mM which was more marked at 50 mM.8 Alloxanate (10 mM) strongly inhibited both basal and secretin-stimulated adenylate cyclase activity.9 It is concluded that the effects of nicotinic acid, alloxanate and imidazole on pancreatic secretion are not mediated entirely through their effects on the adenylate cyclase or phosphodiesterase enzyme systems.
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PMID:The effects of alloxanate, nicotinic acid and imidazole on secretory processes and the activities of adenylate cyclase and 3',5'-AMP phosphodiesterase in cat pancreas. 20 Feb 97

It was established that microvessels of a bovine cortex exhibit significant cyclic 3',5'-adenosine monophosphate phosphodiesterase (cAMP PDE) and cyclic 3',5'-guanosine monophosphate phosphodiesterase (cGMP PDE) activities. These activities are dependent on the presence of Mg2+. Absence of Ca2+ was virtually without effect. When both Mg2+ and Ca2+ were absent, PDE activities increased compared with activities observed in the absence of Mg2+. Xanthines (caffeine, theobromine, and theophylline) were better inhibitors of cAMP PDE than of cGMP PDE. Imidazole, in very high concentration (1 X 10(-2) M) only, exhibited PDE stimulatory activity at high concentrations of both substrates. Otherwise, it exhibited PDE-inhibitory properties.
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PMID:Cyclic 3',5'-adenosine monophosphate phosphodiesterase (cAMP PDE) and cyclic 3',5'-guanosine monophosphate phosphodiesterase (cGMP PDE) in microvessels isolated from bovine cortex. 23 43

Methylxanthines (aminophylline and caffeine) and imidazole, substances with an opposite action on phosphodiesterase (PDE), were found to contract the terminal ileum and to potentiate nerve-mediated responses--contractions elicited by electrical stimulation (ES) at 3 Hz and 30 Hz. Imidazole-induced contractions which were partly reduced by atropine, potentiated both responses to ES to about the same extent, and enhanced contractility of the preparation to histamine and potassium. The action of imidazole on the terminal ileum could be related to its influence on PDE in the smooth muscle. The effects of aminophylline and caffeine were found to be more complex, possibly involving some mechanisms other than inhibition of PDE. They produced atropine-sensitive contractions of the terminal ileum, which were potentiated by physostigmine and strongly depressed by hemicholinium. In the presence of atropine, they potentiated ES-induced contractions, particularly those elicited by ES at 30 Hz, which are thought to be of adrenergic origin. Both actions appeared to be due to presynaptic effects -- activation of cholinergic and adrenergic neurons in the intestinal wall, possibly by enhanced influx of calcium, and facilitated release of acetylcholine and noradrenaline. Aminophylline, in concentrations which potentiated nerve-mediated contractions elicited by ES, did not affect direct smooth muscle-contracting action of drugs. Higher concentrations of aminophylline, above 0.1 mM, were found to inhibit histamine- and noradrenaline-induced contractions presumably due to inhibition of PDE in the smooth muscle and subsequent elevation of cAMP levels.
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PMID:Action of methylxanthines and imidazole on the contractility of the terminal ileum of the guinea pig. 83 69

The treatment in vitro of mouse bone marrow cells with 4-methylhistamine triggered the hematopoietic stem cell (CFU-S) from the G0 state into the S-phase of the cell cycle. In contrast, 2-methylhistamine had no such effect. Metiamide antagonized the effects of low concentrations of 4-methylhistamine. Antagonism by metiamide was reversed by high concentrations of 4-methylhistamine. Imidazole, and activator of phosphodiesterase, also suppressed the cell-cycle effects of 4-methylhistamine. The latter findings suggests that cyclic nucleotides may mediate in the stem cell response to 4-methylhistamine. Blocking the metabolism of endogenous histamine with a combination of aminoguanidine and chloroquine also initiated DNA synthesis in the bone marrow stem cell. Metiamide antagonized the effects of the aminoguanidine/chloroquine combination. These experiments associate a histamine H2-receptor with the hematopoietic stem cell. They also suggest that, if available, endogenous histamine can initiate cell-cycle changes in the pluripotent bone marrow stem cell.
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PMID:Mechanism for histamine H2-receptor induced cell-cycle changes in the bone marrow stem cell. 89 73

In experiments on male albino rats and mice a study is made of the effects of imidazol which is a phosphodiesterase stimulator, papaverine which inhibits phosphodiesterase and histamine which stimulates adenylate cyclase, on the convulsive-seizure reactivity. The substances are introduced intraventricularly and intracerebroventricularly, imidazol also intraperitoneally in different doses and at different intervals before the convulsive agent. Electrical, pentylenetetrazol (Cor) and strychnine convulsion models are used. The effect of imidazol on the spontaneous cortical bioelectrical activity is studied throuth its i. v. administration in rabbits. Imidazol markedly increases the convulsive reactivity, and in large doses it alone results in electrographic and motor convulsions. Paperine slightly lowers the convulsive-seizure reactivity only in pentylenetetrazol convulsions. The results obtained and their comparison with the results of previous experiments of ours with other drugs affecting the cyclic adenosinemonophosphate (cAMP) system, such as lithium, haloperidol, caffeine and theophyline, do not permit to assume a considerable significance of the influence of these substances (in the doses tested) on the cAMP system in the mechanisms of their effects on the convulsive-seizure reactivity.
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PMID:Experimental study of the effects of imidazol, papaverine and histamine on convulsive-seizure reactivity. 101 6

Adenosine 3',5'-cyclic monophosphate (cAMP) phosphodiesterase activity in crude guinea-pig superior cervical ganglion homogenates was assayed under a variety of experimental conditions. Two forms of cAMP phosphodiesterase were found, one with high and the other with low affinity for the substrate. The Km values were about 1 and 110 microM respectively. Imidazole slightly but constantly stimulated the former enzyme form over a wide range of concentrations and 1-methyl-3-isobutylxanthine was a weak competitive inhibitor with a Ki value of 90 microM. Low affinity cAMP phosphodiesterase activity was increased by calmodulin and Ca2+. This stimulation was not observed in the presence of trifluoperazine, a specific inhibitor of calmodulin. On the other hand, neither [D-Ala2]met-enkephalinamide nor prostaglandin E2, alone or in combination, influenced high affinity cAMP phosphodiesterase.
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PMID:Some properties of adenosine 3',5'-cyclic monophosphate phosphodiesterase in the superior cervical ganglion of the guinea pig. 243 35


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