Specific antagonism of adenosine‐induced bronchoconstriction in asthma by oral theophylline.

Mann, J. S.; Holgate, S. T.

doi:10.1111/j.1365-2125.1985.tb02696.x

Cited by 99 publications

(32 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mechanism of bronchoconstriction is indirect, and involves release of histamine and leukotrienes from airway mast cells [32,33]. The bronchoconstrictor effect of adenosine is prevented by therapeutic concentrations of theophylline [34]. This confirms the fact that theophylline is capable of antagonizing the effects of adenosine at therapeutic concentrations, but does not necessarily indicate that this is important for its anti-asthma effect.…”

Section: Adenosine Receptor Antagonismsupporting

confidence: 68%

“…However, the bronchodilator effect of theophylline in chronic asthma is small in comparison with β-agonists. Several studies have demonstrated a small protective effect of theophylline on histamine, methacholine, distilled water or exercise challenge [34,[53][54][55][56][57]. This protective effect does not correlate well with any bronchodilator effect, and it is interesting that in some studies the protective effect of theophylline is observed at plasma concentrations of < 10 mg·l -1 [54,55].…”

Section: Airway Smooth Muscle Effectsmentioning

confidence: 99%

See 1 more Smart Citation

Theophylline in the management of asthma: time for reappraisal?

Barnes¹,

Pauwels²

1994

Eur Respir J

250

107

View full text Add to dashboard Cite

T Th he eo op ph hy yl ll li in ne e i in n t th he e m ma an na ag ge em me en nt t o of f a as st th hm ma a: : t ti im me e f fo or r r re ea ap pp pr ra ai is sa al l? ?P.J. Barnes*, R.A. Pauwels** Theophylline is now considered to be a bronchodilator, but it is increasingly recognized that theophylline has other anti-asthma activities, which may be more important. Theophylline, even at low plasma concentrations, inhibits the late asthmatic reaction following allergen challenge. These clinical pharmacological observations are substantiated by experimental animal and in vitro data showing that theophylline has several anti-inflammatory activities relevant to asthma. These include the inhibition of cytokine synthesis and release, the inhibition of inflammatory cell activation and microvascular leakage, and the prevention of airway hyperresponsiveness induced by airway inflammation. Theophylline appears to have immunomodulatory effects, even at relatively low plasma concentrations.Based on these considerations, theophylline can be regarded as a useful alternative to other anti-inflammatory drugs for the chronic treatment of mild to moderate asthma. Theophylline should be used at lower doses to achieve plasma concentrations of 5-10 mg·l -1 , which will avoid the risk of side-effects.Further studies are required to evaluate the role of low-dose theophylline as an adjunct to low-dose inhaled steroids in the management of chronic asthma. It may now be appropriate to re-evaluate the role of theophylline in asthma management.

show abstract

Section: Adenosine Receptor Antagonismsupporting

confidence: 68%

Section: Airway Smooth Muscle Effectsmentioning

confidence: 99%

Theophylline in the management of asthma: time for reappraisal?

Barnes¹,

Pauwels²

1994

Eur Respir J

250

107

View full text Add to dashboard Cite

show abstract

“…Theophylline, a nonselective adenosine receptor antagonist, selectively (relative to histamine) inhibited adenosine-induced bronchoconstriction at doses generating plasma concentrations that are insufficient to inhibit phosphodiesterases but well above those needed to block adenosine receptors (22). Moreover, both rebound hyperresponsiveness to adenosine and exacerbation of symptoms have been reported when chronic theophylline therapy was withdrawn (36).…”

mentioning

confidence: 99%

Characterization of adenosine receptor(s) involved in adenosine-induced bronchoconstriction in an allergic mouse model

Fan

Qin

Mustafa

2003

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

Fan, Ming, Weixi Qin, and S. Jamal Mustafa. Characterization of adenosine receptor(s) involved in adenosine-induced bronchoconstriction in an allergic mouse model. Am J Physiol Lung Cell Mol Physiol 284: L1012-L1019, 2003. First published January 17, 2003 10.1152/ajplung.00353.2002We recently reported that adenosine caused bronchoconstriction and enhanced airway inflammation in an allergic mouse model. In this study, we further report the characterization of the subtype of adenosine receptor(s) involved in bronchoconstriction. 5Ј-(N-ethylcarboxamido)adenosine (NECA), a nonselective adenosine agonist, elicited bronchoconstriction in a dose-dependent manner. Little effects of N 6 -cyclopentyladenosine (A1-selective agonist) and 2-p-(2-carboxyethyl)phenethylamino-5Ј-Nethylcarboxamidoadenosine (A2A-selective agonist) compared with NECA were observed in this model. 2-Chloro-N 6 -(3-iodobenzyl)-9-[5-(methylcarbamoyl)-␤-D-ribofuranosyl]adenosine, an A3-selective receptor agonist, produced a dose-dependent bronchoconstrictor response, which was blocked by selective A3 antagonist 2,3-diethyl-4,5-dipropyl-6-phenylpyridine-3-thiocarboxylate-5-carboxylate (MRS1523). However, MRS1523 only partially inhibited NECA-induced bronchoconstriction. Neither selective A1 nor A2A antagonists affected NECA-induced bronchoconstriction. Enprofylline, a relatively selective A2B receptor antagonist, blocked partly NECA-induced bronchoconstriction. Furthermore, a combination of enprofylline and MRS1523 completely abolished NECA-induced bronchoconstrictor response. Using RT-PCR, we found that all four adenosine receptor subtypes are expressed in control lungs. Allergen sensitization and challenge significantly increased transcript levels of the A2B and A3 receptors, whereas the A1 receptor message decreased. No change in transcript levels of A2A receptors was observed after allergen sensitization and challenge. These findings suggest that A2B and A3 adenosine receptors play an important role in adenosine-induced bronchoconstriction in our allergic mouse model. Finally, whether the airway effects of the receptor agonists/antagonists are direct or indirect needs further investigations. adenosine agonists; adenosine antagonists; mouse lung; asthma AMONG THE MANY ACTIONS of adenosine, several lines of evidence suggest a contribution of adenosine to the pathophysiology of asthma. Adenosine is present in high concentrations in the bronchoalveolar lavage fluid of asthmatics (8). Airway preparations from allergic asthmatic subjects are more sensitive to the contractile responses of adenosine and related analogs (4). Inhaled adenosine causes bronchoconstriction in asthmatics and allergic nonasthmatics compared with normal subjects (24).The response of the asthmatic airways to adenosine involves the activation of extracellular adenosine receptor(s). Theophylline, a nonselective adenosine receptor antagonist, selectively (relative to histamine) inhibited adenosine-induced bronchoconstriction at doses generating plasma concentrations that are insuffic...

show abstract

“…Administration by inhalation of adenosine, or its precursor AMP, induces bronchospasm in patients with asthma and COPD, but not in normal controls (3,4). Adenosine-induced bronchoconstriction is most likely mediated by activation of mast cells because this effect is blocked not only by adenosine receptor antagonists (5), but also by selective H 1 blockers (6, 7) and chromolyn sodium (8). Inhaled adenosine has been shown to increase levels of mast cell mediators such as histamine and tryptase in bronchoalveolar lavage fluid from asthmatics (9).…”

mentioning

confidence: 99%

Adenosine-Activated Mast Cells Induce IgE Synthesis by B Lymphocytes: An A2B-Mediated Process Involving Th2 Cytokines IL-4 and IL-13 with Implications for Asthma

Ryzhov

Goldstein

Matafonov

et al. 2004

The Journal of Immunology

168

130

View full text Add to dashboard Cite

Adenosine provokes bronchoconstriction in asthmatics through acute activation of mast cells, but its potential role in chronic inflammation has not been adequately characterized. We hypothesized that adenosine up-regulates Th2 cytokines in mast cells, thus promoting IgE synthesis by B lymphocytes. We tested this hypothesis in human mast cells (HMC-1) expressing A2A, A2B, and A3 adenosine receptors. The adenosine analog 5′-N-ethylcarboxamidoadenosine (NECA) (10 μM) increased mRNA expression of IL-1β, IL-3, IL-4, IL-8, and IL-13, but not IL-2 and IFN-γ. Up-regulation of IL-4 and IL-13 was verified using RT-PCR and ELISA; 10 μM NECA increased IL-13 concentrations in HMC-1 conditioned medium 28-fold, from 7.6 ± 0.3 to 215 ± 4 pg/ml, and increased IL-4 concentrations 6-fold, from 19.2 ± 0.1 to 117 ± 2 pg/ml. This effect was mediated by A2B receptors because neither the selective A2A agonist 2-p-(2-carboxyethyl)phenethylamino-NECA nor the selective A3 agonist N6-(3-iodobenzyl)-N-methyl-5′-carbamoyladenosine reproduced it, and the selective A2B antagonist 3-isobutyl-8-pyrrolidinoxanthine prevented it. Constitutive expression of CD40 ligand on HMC-1 surface was not altered by NECA. Human B lymphocytes cocultured for 12 days with NECA-stimulated HMC-1 produced 870 ± 33 pg IgE per 106 B cells, whereas lymphocytes cocultured with nonstimulated HMC-1, or cultured alone in the absence or in the presence of NECA, produced no IgE. Thus, we demonstrated induction of IgE synthesis by the interaction between adenosine-stimulated mast cells and B lymphocytes, and suggest that this mechanism is involved in the amplification of the allergic inflammatory responses associated with asthma.

show abstract

Specific antagonism of adenosine‐induced bronchoconstriction in asthma by oral theophylline.

Cited by 99 publications

References 20 publications

Theophylline in the management of asthma: time for reappraisal?

Theophylline in the management of asthma: time for reappraisal?

Characterization of adenosine receptor(s) involved in adenosine-induced bronchoconstriction in an allergic mouse model

Adenosine-Activated Mast Cells Induce IgE Synthesis by B Lymphocytes: An A2B-Mediated Process Involving Th2 Cytokines IL-4 and IL-13 with Implications for Asthma

Contact Info

Product

Resources

About