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)

A clinical study was conducted to evaluate the role of PGs (prostaglandins) and cyclic AMP in the regulation of the contractility and pharmacologic reactivity of guinea pig and human ovaries in vitro. Ovarian contractility results with the various substances tested are graphed. Imidazole, acetylcholine, phenylephrine PGF2alpha, and methyl PGF2alpha increased ovarian contractility of guinea pig and human ovaries in vitro. Aminophylline suppressed this effect. Indomethacin inhibited ovarian contractions. PGF2alpha and its methyl derivative reversed this inhibitory effect of indomethacin. PGE2 decreased the amplitude and frequency of the spontaneous and PGF2alpha-induced contractions. The effect of certain of the substances was dose-dependent. The study results show that aminophylline, a phosphodiesterase inhibitor, is a potent relaxant of guinea pig ovary contraction in vitro. This inhibitory effect is probably caused by the accumulation of cyclic AMP. The ovarian activation caused by imidazole, on the other hand, is probably caused from an increased rate of cyclic AMP destruction. Thus, compounds interfering with cyclic AMP and PG metabolism effect ovarian contractility in vitro.
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PMID:Effects of aminophylline, imidazole and indomethacin on spontaneous and prostaglandin induced ovarian contractions in vitro. 0 82

Blood induced acute and chronic cerebral vasospasm were studied in Rhesus monkeys by serial angiography. Two vasoactive agents were evaluated. In acute spasm, phosphodiesterase inhibition by Aminophylline consistently reversed the vasospasm. This agent alone was ineffective in chronic spasm and required the addition of Isoproterenol to produce reversal of vasospasm. It is proposed that cerebral vasospasm may be associated with a decrease of intracellular c-AMP in vascular smooth muscle which can be reversed by manipulation of the enzyme pathway involved. It is further proposed that c-AMP is a basic common pathway through which adrenergic vascular reactivities are mediated.
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PMID:Experimental cerebral vasospasm and cyclic adenosine monophosphate (c-AMP). 16 52

Fetal lung cyclic AMP phosphodiesterase, cyclic AMP, phosphatidyl choline, and incorporation of precursors into phosphatidyl choline were measured in rabbits after maternal administration of hydrocortisone phosphate and aminophylline. Both agents inhibited lung phosphodiesterase activity and augmented cyclic AMP concentrations (Table 1). Aminophylline administration was associated with a significant increase in lung saturated phosphatidyl choline (Table 2). Incorporation of [14C] choline and [3H] methionine was increased by both aminophylline and hydrocortisone (Table 3).
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PMID:Role of adenosine 3', 5'-monophosphate in maturation of fetal lungs. 17 50

The effect of five phosphodiesterase (PDE) inhibitors (papaverine, IBMX, theophyllamine, dipyridamol and M & B 22,948) was studied on adenylate cyclase and on cyclic nucleotide phosphodiesterase activities in extracts of rat caudate nucleus. For comparison the effect on DA turnover and on turning behaviour in rats with unilateral lesions of the nigro-neostriatal DA nerurons was studied. Cyclic AMP PDE was inhibited by papaverine, dipyridamol, IBMX, M & B 22,948 and theophyllamine in that order of potency. Cylcic GMP PDE was inhibited by IBMX, papaverine, M & B 22,948 and theophyllamine, but not by dipyridamol. Basal adenylate cyclase washigher if assayed in the presence of papaverine or dipyridamol than if theophyllamine or IBMX was present. The degree of stimulation caused by DA was not significantly influenced by the PDE inhibitors. Papaverine and dipyridamol enhanced DA disappearance in the caudate nucleus and the tuberculum accumbens, but not in the median eminence. Caffeine had no significant effect. Papaverine (1-28 mg/kg) had no signigicant effect on L-dopa (5 mg/kg)-induced turning, and actually inhibited turning induced by the combination of L-dopa (10 mg/kg) and atropine (5 mg/kg). The other four PDE inhibitors all potentiated L-dopa-induced turning. Theophyllamine (20 mg/kg) and IBMX (5 mg/kg) even caused turning when given alone. The data are compatible with the opinion that PDE inhibition leads to an enhanced effect of DA in the caudate nucleus. However, the results also demonstrate that several of the PDE inhibitors have effects on central DA mechanisms that are difficult to explain solely on the basis of PED inhibition.
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PMID:Effect of some phosphodiesterase inhibitors on central dopamine mechanisms. 18 7

The binding of [3H]dexamethasone-receptor complex from rat liver cytosol to isolated nuclei or DNA-cellulose can be greatly enhanced at low temperature by the presence of theophylline. Aminophylline and caffeine can mimic this effect; however, papaverine and 1-methyl-3-isobutylxanthine, at concentrations inhibitory to phosphodiesterase, are without effect on glucocorticoid receptor binding to DNA. Furthermore, theophylline can be added when adenosine 3':5'-monophosphate-(cAMP) hydrolysis is already complete and still enhance DNA binding. These results imply that this effect of theophylline is independent of its known effect on cAMP levels. Activation by methylxanthines does not alter the sedimentation of the glucocorticoid-receptor complex in sucrose gradients but does alter the pI and in this respect brings about changes resembling those which occur upon activation by heat. Recently we have shown that pyridoxal phosphate inhibits the binding of heat-activated receptor to DNA-cellulose. Similarly, we have shown here that pyridoxal phosphate also inhibits the DNA-cellulose binding of theophylline-treated receptor. The presence of theophylline also enhances the rate of binding of [3H]dexamethasone to the receptor and increases its apparent affininty for the steroid. The data suggest that the effect of theophylline is on some cytosolic component, perhaps the receptor itself. Enhanced DNA binding as a result of exposure to theophylline at low temperature can also be demonstrated using the glucocorticoid receptor of kidney, thymus and Reuber H35 cells.
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PMID:Effect of methylxanthines on binding of the glucocorticoid receptor to DNA-cellulose and nuclei. 20 67

Agents known to increase intracellular levels of cyclic 3', 5'-adenosine monophosphate (cyclic AMP) were examined for their effect on tissue factor generation by mononuclear cells cultured with E. coli endotoxin. Aminophylline, an inhibitor of phosphodiesterase, and epinephrine, a beta-adrenergic agent, showed an inhibitory effect, and these effects were reversible. Moreover, dibutyryl cyclic AMP also exhibited the effect. Dibutyryl cyclic GMP, however, did not enhance the tissue factor generation by mononuclear cells. On the basis of these observations, it was concluded that the phenomenon of tissue factor generation by mononuclear cells is a biological event, and that intracellular cyclic AMP has a possible role in modulating this phenomenon.
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PMID:Prevention of tissue factor generation in mononuclear cells by agents known to increase intracellular cyclic AMP. 21 34

The glycogen content of fetal rat lung declines coincident with increased pulmonary phospholipid synthesis. Aminophylline, a methylxanthine cyclic adenosine 3',5' monophosphate (AMP) phosphodiesterase inhibitor, and cyclic AMP augment fetal lung phospholipid synthesis. Because lung glycogen breakdown may contribute to pulmonary phospholipid synthesis, the effects of aminophylline and cyclic AMP on glycogen metabolism were studied in explants of 19 day fetal rat lung in organ culture. Treatment with aminophylline or dibutyryl cyclic AMP for 24 hr, resulted in a 25% (P less than 0.025) and 75% (P less than 0.001) decrease, respectively, in the glycogen content of the explants. Glycogen synthase I activity was reduced by 32% in aminophylline treated cultures (P less than 0.025) and 25% in cyclic AMP treated cultures (P less than 0.025). The percent of total synthase in the active form was significantly reduced in all treated cultures. Neither aminophylline nor cyclic AMP treatment resulted in significant changes in glycogen phosphorylase a or total phosphorylase activity.
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PMID:Influence of aminophylline and cyclic AMP on glycogen metabolism in fetal rat lung in organ culture. 23 Apr 47

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 in vivo effects of GABA-ergic drugs on the activity of serotonin N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT), two enzymes involved in melatonin biosynthesis, were investigated in light-exposed chicken retina. The ip administration of muscimol and baclofen (direct agonists of GABA-A and GABA-B receptors, respectively), aminooxyacetic acid (an inhibitor of GABA transaminase), and nipecotic acid (an inhibitor of GABA reuptake), significantly increased the retinal NAT activity by 50-100%. Similar rises in NAT activity were observed following intraocular treatment of ether-anesthetized chickens with muscimol, baclofen and GABA. In contrast to NAT, there was no effect of the tested drugs on the retinal HIOMT activity. Aminophylline (a phosphodiesterase inhibitor) markedly elevated the retinal NAT activity, and a combined treatment with the GABA-ergic drugs and aminophylline resulted in additive effects. The actions of both muscimol and baclofen were antagonized by picrotoxin and bicuculline (two GABA-A receptor blockers), whereas the effect of baclofen was not changed by a selective GABA-B receptor blocker, CGP 35,348. Melatonin given ip significantly raised NAT activity, and its combination with muscimol further stimulated the enzyme. Picrotoxin and bicuculline given to chickens during the dark phase of 12 h light--12 h dark illumination cycle significantly suppressed the nocturnal NAT activity in retina. Neither GABA nor muscimol and baclofen significantly affected basal and forskolin (1 microM)-stimulated adenylate cyclase activity in vitro in light-exposed chicken retina. It is concluded that a GABA signal (acting through type A of GABA receptors) plays an important role in a complex mechanism regulating the rhythmic melatonin biosynthesis in vertebrate retina.
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PMID:The role of GABA-ergic signal in the regulation of melatonin biosynthesis in vertebrate retina. 130 60

This study was undertaken to determine whether isozyme-specific inhibitors of cAMP-selective phosphodiesterases (PDEs) induce bronchodilation without the cardiovascular side effects known to be produced by nonselective PDE inhibitors. The abilities of PDE inhibitors to reverse the bronchoconstriction induced by serotonin in a beta-blocked anesthetized dog were compared simultaneously with their effects on cardiac contractile force (+dP/dt), heart rate and blood pressure. Aminophylline and enprofylline, two antiasthma drugs with nonselective PDE inhibitory activity, produced dose-dependent (ED50S = 2.3 and 0.58 mg/kg, respectively) and complete (95-100%) bronchodilation accompanied by profound increases in cardiac force, tachycardia and decreases in blood pressure. Similar effects were observed with forskolin, a potent adenylate cyclase activator. Imazodan and CI-930 (inhibitors of the cGMP-inhibitable cAMP-selective PDE isozyme designated PDE-III) induced pulmonary and cardiovascular effects virtually identical to the nonselective PDE inhibitors, but with greater potency (ED50S = 0.02 and 0.04 mg/kg). In contrast, rolipram and Ro 20-1724 (inhibitors of a cGMP-insensitive cAMP-selective PDE isoform commonly designated PDE-IV) induced bronchodilation in the dog (ED50S = 0.007 and 0.63 mg/kg, respectively) without causing significant changes in cardiac force or heart rate, even after predosing dogs with forskolin. However, rolipram and Ro 20-1724 were less efficacious than the other inhibitors in that they induced only partial (50-60%) bronchodilation. The results suggest that canine respiratory muscle tension is regulated by both PDE-III and PDE-IV. Inhibitors of PDE-IV produce bronchodilation in the described model with minimal concomitant cardiac side effects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bronchial vs. cardiovascular activities of selective phosphodiesterase inhibitors in the anesthetized beta-blocked dog. 203 17


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