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

---

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

The binding of various adenosine receptor ligands and of [3H]diazepam, as well as their inhibition of methylxanthines, have been studied in human brain cerebral cortex membranes. Caffeine and theophylline competitively inhibit binding of [3H]cyclohexyladenosine, [3H]diethylphenylxanthine, [3H]phenylisopropyladenosine and [3H]diazepam. Both caffeine and theophylline are more potent as inhibitors of adenosine receptor ligand binding compared to [3H]diazepam binding. Theophylline was more potent than caffeine in its ability to compete with adenosine receptor ligand binding while the reverse was true for [3H]diazepam binding. The meaning of these results for the mode of action of methylxantine is discussed.
...
PMID:Effects of caffeine and theophylline on adenosine and benzodiazepine receptors in human brain. 628 66

1 The purpose of this study was to determine whether the adenosine receptor that mediates a decrease in the force of contraction of the guinea-pig atrium is of the A1- or A2-sub-type. 2 Concentration-response curves to adenosine and a number of 5'- and N6-substituted analogues were constructed and the order of potency of the purines was: 5'-N-cyclopropylcarboxamide adenosine (NCPCA) = 5'-N-ethylcarboxamide adenosine (NECA) greater than N6cyclohexyladenosine (CHA) greater than L-N6-phenylisopropyl adenosine (L-PIA) = 2-chloroadenosine- greater than adenosine greater than D-N6-phenylisopropyl adenosine (D-PIA). 3 The difference in potency between the stereoisomers D- and L-PIA was over 100 fold. 4 The adenosine transport inhibitor, dipyridamole, potentiated submaximal responses to adenosine but had no significant effect on those evoked by the other purines. 5 Theophylline antagonized responses evoked by all purines, and with D-PIA revealed a positive inotropic effect that was abolished by atenolol. 6 The results indicate the existence of an adenosine A1-receptor in the guinea-pig atrium.
...
PMID:Evidence for an A1-adenosine receptor in the guinea-pig atrium. 629 47

Theophylline-7-riboside was evaluated as a partial agonist for rat adenosine receptors. Radioligand binding experiments were performed on both A1 and A2a adenosine receptors, using several methodologies to discriminate between agonists and antagonists. Mainly from thermodynamic data it was concluded that on A1 receptors theophylline-7-riboside had characteristics intermediate between full agonists, such as N6-cyclopentyladenosine, and full antagonists, such as the xanthines. The partial agonistic behaviour of theophylline-7-riboside was further explored in second messenger studies in intact cells. In FRTL-5 rat thyroid cells theophylline-7-riboside behaved as a partial agonist for A1 receptors, slightly inhibiting forskolin-stimulated cyclic AMP levels. The implications of these biochemical findings were further analysed in in vivo pharmacology. The infusion of theophylline-7-riboside in conscious, normotensive rats led to marked changes in cardiovascular parameters, although less outspoken than observed with full agonists for either A1 or A2a receptors. The concomitant determination of the blood concentrations of theophylline-7-riboside and its metabolite theophylline allowed the estimation of in vivo pharmacokinetic and pharmacodynamic parameters. Thus, the EC50 value of theophylline-7-riboside for lowering the mean arterial pressure was 47 +/- 12 micrograms/ml blood. The short duration of action of theophylline-7-riboside makes it improbable that its metabolite theophylline interferes with its effects. In conclusion, theophylline-7-riboside is one of the first partial agonists for adenosine receptors. It may serve as a tool in further investigations of adenosine receptor partial agonism.
...
PMID:Partial agonism of theophylline-7-riboside on adenosine receptors. 770 21

Radiographic contrast media (CM) can induce renal failure and this may serve as an experimental model of acute renal failure (ARF). One vasoactive factor likely to be involved in ARF is adenosine. In a double-blind, placebo-controlled study we investigated the effect of theophylline (TP), an adenosine receptor antagonist, regarding changes in renal hemodynamics induced by CM. Thirty-nine patients who received 100 ml of a non-ionic low osmolar CM (iopromide) were studied for changes in GFR and RPF by continuous inulin and PAH clearance before and until four hours after CM application. Forty-five minutes before the application of CM, patients were randomized and received either theophylline (5 mg/kg body wt) or the vehicle and placebo (saline) intravenously in a blinded manner. We additionally measured the creatinine clearance on the day before and two days after CM application. Sodium excretion, N-acetyl-beta-glucosaminidase (NAG) excretion, plasma renin activity (PRA) and aldosterone levels were also measured before and after CM application. Theophylline levels were within the therapeutic range in patients of the theophylline group during and four hours after CM application (59.0 +/- 10.6 mumol/liter and 40.1 +/- 10.9 mumol/liter). GFR, measured by inulin clearance significantly declined under CM application in patients without TP application (N = 19; 88 +/- 40 to 75 +/- 32 ml/min/1.72 m2; P < 0.01). In the group of patients receiving theophylline (N = 18) the GFR remained constant (75 +/- 26 vs. 78 +/- 33 ml/min/1.72 m2).(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Adenosine antagonist theophylline prevents the reduction of glomerular filtration rate after contrast media application. 807 55

The duration of gasping has no normal distribution, so nonparametric statistic criteria should be used. Three adenosine receptor agonists have a highly cerebro-protective effect which decreases in the order: N-ethylcarboxamide adenosine > > cyclohexyl adenosine > adenosine. Theophylline completely blocks these effects. Thus, they act through adenosine receptors. Adenosine receptor agonist are likely to protect themselves neurons.
...
PMID:[The comparative characteristics and receptor mechanism of the effect of adenosine-receptor agonists in total cerebral ischemia]. 811 Dec 86

Isometric exercise increases sympathetic nerve activity and blood pressure. This exercise pressor reflex is partly mediated by metabolic products activating muscle afferents (metaboreceptors). Whereas adenosine is a known inhibitory neuromodulator, there is increasing evidence that it activates afferent nerves. We, therefore, examined the hypothesis that adenosine stimulates muscle afferents and participates in the exercise pressor reflex in healthy volunteers. Intraarterial administration of adenosine into the forearm, during venous occlusion to prevent systemic effects, mimicked the response to exercise, increasing muscle sympathetic nerve activity (MSNA, lower limb microneurography) and mean arterial blood pressure (MABP) at all doses studied (2, 3, and 4 mg). Heart rate increased only with the highest dose. Intrabrachial adenosine (4 mg) increased MSNA by 96 +/- 25% (n = 6, P < 0.01) and MABP by 12 +/- 3 mmHg (P < 0.01). Adenosine produced forearm discomfort, but equivalent painful stimuli (forearm ischemia and cold exposure) increased MSNA significantly less than adenosine. Furthermore, adenosine receptor antagonism with intrabrachial theophylline (1 microgram/ml forearm per min) blocked the increase in MSNA (92 +/- 15% vs. 28 +/- 6%, n = 7, P < 0.01) and MABP (38 +/- 6 vs. 27 +/- 4 mmHg, P = 0.01) produced by isometric handgrip (30% of maximal voluntary contraction) in the infused arm, but not the contralateral arm. Theophylline did not prevent the increase in heart rate produced by handgrip, a response mediated more by central command than muscle afferent activation. We propose that endogenous adenosine contributes to the activation of muscle afferents involved in the exercise pressor reflex in humans.
...
PMID:Role of adenosine in the sympathetic activation produced by isometric exercise in humans. 816 67

Theophylline, as used for the treatment of asthma and chronic obstructive pulmonary disease, may have several effects, including direct bronchodilation, improvement in diaphragmatic and ciliary function, and possibly immune modulation. In this study, we quantified the capacity for theophylline to inhibit natural killer (NK) cells and investigated the mechanism(s) that mediate this inhibition. Theophylline at 10 micrograms/ml and 20 micrograms/ml inhibited the tumoricidal activity of isolated peripheral blood lymphocytes (PBL) by 19 +/- 5% and 36 +/- 6%, respectively (n = 6). Using fluorescence-activated cell sorting, we purified NK cells from PBL and tested theophylline's effects on the kinetics of tumor lysis (Vmax) and on tumor binding. Theophylline at 20 micrograms/ml reduced Vmax by 40 +/- 9% but had no effect on tumor binding. We compared the effects of theophylline, which is both a phosphodiesterase (PDE) inhibitor and an adenosine receptor (AdR) antagonist, with agents that range from relatively pure AdR antagonists to pure PDE inhibitors. Inhibition of NK activity occurred only with PDE inhibitors. We also extracted lymphocyte PDE and observed a direct correlation (r2 = 0.99) between theophylline's activity as a PDE inhibitor and its capacity to inhibit NK activity. These results suggest that theophylline inhibits NK cytotoxicity through its activity as a PDE inhibitor. The clinical relevance of these findings awaits further study.
...
PMID:Inhibition of natural killer cell activity by therapeutic levels of theophylline. 825 97

The present studies were undertaken to assess the effects of 5'-N-ethylcarboxamideadenosine (NECA), an adenosine analogue, on erythropoietin (Epo) production. NECA (0.05 and 0.1 mumol/kg i.v.) produced significant increases in serum Epo levels (368.8 +/- 56.1 and 384.6 +/- 45.9 mU/ml, respectively) in exhypoxic polycythemic mice after a four hour exposure to hypoxia when compared with hypoxia controls (133.2 +/- 18.2 mU/ml). The hypoxic kidney Epo levels were 46.4 +/- 13.4 mU/kg kidney which were significantly higher than normoxic kidney Ep levels (< 1.24 mU/kg kidney). Theophylline (20 mg/kg i.p.), an adenosine receptor antagonist, significantly inhibited the stimulatory effects of NECA on serum Epo levels. In vitro cultures of an Epo producing hepatocellular carcinoma (Hep3B) cell line with NECA (> or = 10(-6) M) for 20 hours under hypoxic conditions (1% O2) produced significant increases in medium levels of Epo when compared with hypoxia controls. Hepatocellular carcinoma cells treated with NECA at a concentration range of 10(-7) M to 5 x 10(-5) M for one hour in a hypoxic atmosphere also had significantly higher cAMP levels than that of hypoxia controls. Scatchard analyses of [3H]NECA binding to membrane preparations of hepatocellular carcinoma cells showed low affinity binding sites with a dissociation-constant (Kd) of 0.44 microM and a binding capacity of 863 fmol/mg protein. These findings suggest that the increase in Epo production in response to NECA under hypoxic conditions can be attributed, at least in part, to stimulation of adenosine A2 receptors which is coupled to adenylyl cyclase activation.
...
PMID:Effects of 5'-N-ethylcarboxamideadenosine (NECA) on erythropoietin production. 825 50

Freshly drawn blood samples from seven female and seven male healthy donors were used. Arginine8-vasopressin (AVP) effects on platelet aggregation and serotonin (5-HT) release were examined in adenosine-depleted platelet-rich plasma (PRP) and PRP containing normal amounts of plasma adenosine. No significant differences in the plasma adenosine levels were noted between female (208 +/- 90 nM) and male (239 +/- 85 nM) subjects, but significant differences in AVP-induced platelet aggregation and 5-HT release were noted between female and male subjects. In adenosine-depleted PRP, platelets from most female donors could be aggregated irreversibly at low levels of AVP (18 mU/ml, or 42 nM), whereas platelets from most male donors responded poorly and caused only reversible aggregation at much higher AVP levels (108-720 mU/ml PRP or 252-1,680 nM). In contrast, in PRP containing normal amounts of adenosine, AVP response to induce platelet aggregation was much weaker, demonstrating that adenosine acts as a natural modulator of AVP actions. Theophylline and a relatively selective A2 antagonist DMPX (3,7-dimethyl-1-propargylxanthine) attenuate the plasma adenosine effects causing potentiation in AVP activity on platelet aggregation. These studies suggest that agents that can increase plasma adenosine levels (e.g., inhibitors of nucleoside transport and adenosine deaminase), or adenosine receptor antagonists, may have potential therapeutic uses in modulation of AVP actions in the body. Furthermore, the human platelet serves as a suitable pharmacologic model to study interactions between biologically produced adenosine and AVP.
...
PMID:Modulation of vasopressin actions on human platelets by plasma adenosine and theophylline: gender differences. 833 6

1. We describe here the effects of intrathecal selective adenosine receptor agonists on acute and more persistent evoked responses of dorsal horn nociceptive neurones recorded in intact rats anaesthetized with halothane. 2. The effects of the A1 receptor agonist, N6-cyclopentyladenosine and the non-selective agonist 2-chloroadenosine as well as the A2a receptor agonist, 2-p-(2-carboxyethyl) phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride were gauged on the C-, A delta-, A beta-fibre, post-discharge and wind-up responses produced by peripheral tanscutaneous stimulation. The antagonists, theophylline and 8(p-sulphophenyl) theophylline were also tested alone and to reverse the agonist effects. 3. Subcutaneous formalin (5%) was used to produce a more prolonged nociceptive response initiated by peripheral inflammation. 4. Both N6-cyclopentyladenosine and 2-chloroadenosine produced inhibitions of the C-fibre evoked responses, wind-up and post-discharge of the neurones with no significant effects on the A beta responses. By contrast, the A delta evoked responses were facilitated over the same time course and dose-range as the inhibitions. N6-cyclopentyladenosine was more potent and effective than 2-chloroadenosine. In marked contrast to these agonists, the A2a agonist produced only weak non-specific inhibitions. Theophylline and 8(p-sulphophenyl) theophylline alone had no effect on the acute responses but prevented or reversed inhibitory effects of N6-cyclopentyladenosine. 5. The formalin response was markedly inhibited by spinal N6-cyclopentyladenosine with both the acute first phase and more prolonged second phase being dose-dependently inhibited. N6-cyclopentyladenosine was considerably more potent on the formalin response than on the other neuronal measures. 6 The results suggest a role of adenosine Al receptors in the modulation of both acute and inflammatory nociception in the spinal cord.
...
PMID:The roles of spinal adenosine receptors in the control of acute and more persistent nociceptive responses of dorsal horn neurones in the anaesthetized rat. 856 52


<< Previous 1 2 3 4 5 6 7 8 9 Next >>

---