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Query: KEGG:D06103 (Theophylline)
 2,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several previous observations support the hypothesis that increased adenosine production and release mediate, at least in part, the reductions in renal blood flow and glomerular filtration rate in ischemic acute renal failure (ARF). If this hypothesis is correct, dipyridamole should potentiate these changes, since it blocks cellular adenosine uptake, thereby increasing the concentration and potentiating the effects of extracellular adenosine. Moreover, theophylline should block the effects of dipyridamole, since it is an adenosine receptor antagonist. These predictions were tested in three groups of anesthetized rats. All rats were subjected to 30 min of left renal artery occlusion; 30 min after relieving the occlusion, a 45-min clearance period was begun. The control group was given saline i.v.; the two experimental groups received either dipyridamole (24 micrograms X min-1 X kg-1) or dipyridamole plus theophylline i.v. (111 mumol/kg as a prime, 1.1 mumol X min-1 X kg-1 as an infusion). In the control group, the previously ischemic left kidneys exhibited decreased clearances of para-aminohippurate and inulin (CPAH and CIn), filtration fraction (FF), and urine/plasma inulin concentration (U/PIn), and increased urine flow (V), Na excretion (UNaV), and fractional Na excretion (FENa) in comparison with the contralateral right kidney. Dipyridamole pretreatment did not affect the right kidney, but it intensified the reductions in left kidney CPAH, CIn, and FF. Theophylline blocked all these effects of dipyridamole on the left kidney, and increased renal plasma flow (CPAH/PAH extraction), despite a decrease in systemic arterial blood pressure. These results are further support for the hypothesis that adenosine mediates, at least in part, the hemodynamic changes in postischemic ARF in rats.
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PMID:The effect of dipyridamole on the initiation phase of postischemic acute renal failure in rats. 366 62

This study compared the effects of theophylline and adenosine on the contractile activity of respiratory smooth and skeletal muscles in vitro. Studies were performed on isolated strips of tracheal smooth and diaphragmatic skeletal muscle from 22 Hartley strain guinea pigs. The changes in diaphragm and tracheal smooth muscle tension in response to electrical stimulation and histamine-induced contraction, respectively, were assessed over a range of theophylline and adenosine concentrations (10(-7) to 10(-3) M for each). Theophylline increased diaphragmatic tension and reversed histamine-induced smooth muscle contractions in a dose-dependent fashion. Theophylline, however, decreased tracheal tension at concentrations an order of magnitude lower than those that increased diaphragmatic tension. Adenosine mimicked the effect of theophylline on tracheal muscle but had no effect on the force of diaphragm contraction. Moreover, adenosine failed to alter the theophylline dose-response curve for diaphragmatic tension. This study demonstrates that airway smooth muscle is more sensitive than is respiratory skeletal muscle to the effects of theophylline. Furthermore, these data suggest that the effects of theophylline on diaphragm skeletal muscle are not mediated by adenosine receptor blockade.
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PMID:Comparative effects of theophylline and adenosine on respiratory skeletal and smooth muscle. 370 89

The effects of adenosine, adenosine triphosphate (ATP) and adenosine diphosphate (ADP) on ventricular automaticity induced by a local injury have been studied in the isolated right ventricle of the rat. Adenosine in low concentrations (10(-10)--10(-8) M) increased ventricular automaticity but in high concentrations (10(-5)--10(-4) M) decreased it. ATP and ADP decreased consistently ventricular automaticity, ATP being more effective than ADP. Theophylline in a concentration (5 X 10(-4) M) devoid of effect on ventricular automaticity antagonized both the excitatory and the inhibitory effects of adenosine. A high calcium solution (5.4 mM calcium) also prevented both the excitatory and the inhibitory effects of adenosine. The results suggest that adenosine in low concentrations might contribute to ventricular dysrhythmias, and that ATP and ADP as well as high concentrations of adenosine might have antidysrhythmic effects. The effects of adenosine appear to be mediated through calcium-dependent theophylline-sensitive receptors: the high affinity receptor operating the excitatory effect and the low affinity adenosine receptor operating the adenosine inhibitory effect on ventricular automaticity.
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PMID:The effects of adenosine, ATP and ADP on ventricular automaticity induced by a local injury in the isolated right ventricle of the rat. 396 39

The effect on the allergen-induced immediate and late bronchoconstriction of theophylline and enprofylline (3-propylxanthine), a new xanthine derivative with negligible ability to antagonize adenosine, was studied in nine patients with asthma. The patients were challenged three times at weekly intervals with the same dose of allergen. FEV1 and SGaw were followed up to 6 hours after challenge. The drugs were administered intravenously. Placebo was always administered on the first occasion. Theophylline and enprofylline were administered on test days 2 and 3 with a double-blind, randomized crossover technique. One hour before the allergen challenge, a loading dose was administered during 60 minutes followed by a constant infusion during 6 hours. The loading infusion was 7.2 mg/kg of theophylline and 2.7 mg/kg of enprofylline. The maintenance dose was 74 mg/hr and 71 mg/hr, respectively. Both theophylline and enprofylline caused a minor initial bronchodilatation. Theophylline and enprofylline slightly but significantly attenuated the immediate bronchoconstricting reaction after allergen inhalation. Theophylline and enprofylline had a significant attenuating effect on the late bronchial reaction. The mean plasma level of theophylline was 0, 10.8, 10.5, and 10.5 mg/L at 0, 1, 4, and 7 hours after the start of the loading infusion, respectively. The corresponding mean plasma levels of enprofylline were 0, 2.6, 2.7, and 2.7 mg/L. Theophylline and enprofylline caused headache in one patient. Two patients developed nausea and vomiting during the enprofylline infusion. The present data suggest that adenosine receptor antagonism may not be the main mode of action of xanthines in inhibiting bronchoconstriction after single dose antigen challenge.
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PMID:The effect of theophylline and enprofylline on allergen-induced bronchoconstriction. 405 46

Theophylline and other methylxanthines display a large number of biological effects, some of which are clinically important. The effects of these compounds are commonly ascribed to an inhibition of cyclic AMP breakdown. However, it becomes actually evident that another mechanism, namely adenosine receptor antagonism, could be responsible for certain methylxanthine effects. It could be of interest to find new compounds displaying only one of these mechanisms, either phosphodiesterase inhibition or adenosine receptor antagonism. We have studied several synthetic imidazol[1,2a]pyrazines, some of which display theophylline-like pharmacological properties at lower doses than theophylline. We showed that some of these compounds inhibited mitogen-induced [3H]-thymidine uptake by human lymphocytes, which is consistent with increases in cyclic AMP levels: the most efficient compounds were those which were better phosphodiesterase inhibitors than theophylline and poorer adenosine receptor antagonists.
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PMID:Theophylline-like properties of xanthine analogs. 608 21

The effects of adenosine, adenosine triphosphate (ATP) and structural analogues have been studied on glucagon secretion from the isolated perfused pancreas of the rat in the presence of glucose (2.8 mM). Adenosine induced a transient increase of glucagon secretion. This effect was concentration-dependent in the range of 0.165 to 165 microM. ATP also induced an increase, but the effect was no greater at 165 microM than at 16.5 microM. 2-Chloroadenosine, an analogue more resistant to metabolism or uptake systems than adenosine, was more effective. Among the three structural analogues of ATP or ADP studied, beta, gamma-methylene ATP which can be hydrolyzed into AMP and adenosine had an effect similar to adenosine or ATP at the same concentrations (1.65 and 16.5 microM); in contrast alpha, beta-methylene ATP and alpha, beta-methylene ADP (resistant to hydrolysis into AMP and adenosine) were ineffective. Theophylline (50 microM) a specific blocker of the adenosine receptor, suppressed the glucagon peak induced by adenosine, 2-chloroadenosine, ATP and beta, gamma-methylene ATP (1.65 microM). An inhibitor of 5' nucleotidase, alpha, beta-methylene ADP (16.5 microM), reduced the glucagon increase induced by ATP and did not affect the response to adenosine (1.65 microM). These results support the hypothesis of adenosine receptors (P1-purinoceptors) on the pancreatic glucagon secretory cells and indicate that ATP acts after hydrolysis to adenosine.
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PMID:Effects of adenosine, adenosine triphosphate and structural analogues on glucagon secretion from the perfused pancreas of rat in vitro. 609 28

Theophylline (1, 3-dimethylxanthine) and enprofylline (3-propylxanthine) have been examined for effects in the rat. Enprofylline was 3.8 times as potent as theophylline as a tracheal relaxant in vitro, and 1.3 times as potent as theophylline to increase the rate of isolated perfused hearts. An oral dose (5 mg/kg) of enprofylline to rats was almost completely recovered in the urine as unchanged drug, showing that this xanthine is well absorbed and negligibly metabolised. Theophylline (10 and 30 mg/kg p.o.) significantly and dose-dependently increased locomotor activity in rats whereas the same doses of enprofylline were without effect on behaviour. Theophylline ( 5-20 mg/kg p.o.) produced significant and dose-dependent natriuretic and volume diuretic effect with little augmentation of potassium excretion. Enprofylline up to 10 mg/kg was without diuretic effects. At the large dose of 20 mg/kg enprofylline decreased sodium excretion and produced some volume diuresis. It is suggested that lack of diuretic and CNS-stimulant behavioural effects by enprofylline is due to its low ability to antagonise adenosine receptor stimulation. Pharmacodynamic differences between enprofylline and the potent adenosine antagonist theophylline may indicate a functional importance of endogenous adenosine.
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PMID:Tracheal relaxant and cardiostimulant actions of xanthines can be differentiated from diuretic and CNS-stimulant effects. Role of adenosine antagonism? 613 Apr 56

1-Methylisoguanosine, a novel purine isolated from the sponge Tedania digitata (Schmidt) selectively inhibited contractions produced by nerve stimulation in the guinea-pig ileum but was without effect on contractions produced by acetylcholine or histamine. The ED50 for inhibition of nicotine responses or responses to submaximal transmural stimulation was 1.1 mumoles/l. The inhibition of nerve-mediated contractions appeared to be due to inhibition of transmitter release from nerve endings in the ileum, as has been suggested for the action of adenosine. Theophylline antagonized the action of 1-methylisoguanosine and overall the results suggest that 1-methyl-isoguanosine acts at an adenosine receptor in the guinea-pig ileum, but is approximately ten times more potent than adenosine itself. A series of related purines which were resistant to the action of adenosine deaminase were also tested for their effect on the nerve-mediated contractions of guinea-pig ileum and the results compared with the in vivo effect on muscle relaxation in mice. All active purines tested produced results qualitatively similar to those of 1-methylisoguanosine itself.
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PMID:Inhibition of nerve-mediated contractions in isolated guinea-pig ileum by 1-methylisoguanosine, a novel purine from a sponge. 625 32

Theophylline 9-beta-D-riboside and 8-phenyltheophylline were evaluated as presynaptic adenosine receptor antagonists in the rat vas deferens in vitro. Stimulation of presynaptic adenosine receptors, which results in an inhibition of the twitch response to electrical field stimulation, was achieved with 2-chloroadenosine, an adenosine analogue that appears not to be a substrate for the adenosine transport system. The presynaptic inhibitory action of 2-chloroadenosine was antagonized by theophylline (10 and 100 microM) and by 8-phenyltheophylline (10 microM) but not by theophylline 9-beta-D-riboside (100 microM). It is concluded that the addition of a ribose moiety to theophylline does not enhance the antagonist potency of the molecule but actually renders the compound inactive. However, 8-phenyltheophylline is approximately three times more potent than theophylline at presynaptic adenosine receptors.
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PMID:Antagonism of presynaptic adenosine receptors by theophylline 9-beta-D-riboside and 8-phenyltheophylline. 627 73

This study demonstrates the existence of adenosine receptor(s) in a homogeneous population of cultured smooth muscle cells and intact muscle strips from rabbit aorta. Binding assays with 3H-adenosine were performed using the crude microsomal fraction of the cultured cells. Adenosine binding was reversible and displayed a single species of saturable binding sites. The nuclear and soluble fractions showed negligible binding. Adenosine uptake blockers (e.g., nitrobenzylthioinosine, dipyridamole) had no effect on its binding. Theophylline inhibited the binding and the relaxation of aortic strips to adenosine. The data suggest the existence of specific binding sites for adenosine on the surface of aortic smooth muscle cells.
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PMID:Demonstration of a putative adenosine receptor in rabbit aorta. 628 Jul 88


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