Analysis of the bronchoconstrictor responses to adenosine receptor agonists in sensitized guinea-pig lungs and trachea

Thorne, Julian R.; Danahay, Henry; Broadley, Kenneth J.

doi:10.1016/s0014-2999(96)00685-1

Cited by 30 publications

(27 citation statements)

References 23 publications

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“…The same investigators, in a more recent study, questioned the role of A 2B receptors in the bronchoconstrictor responsiveness to adenosine in Brown Norway rats (14). Studies using guinea pigs suggest the existence of a mechanism involving adenosine A 3 receptors (18,38). In another animal model, the animals immunized neonatally with ragweed or house dust mite developed bronchoconstrictor responsiveness to adenosine agonists (1).…”

Section: Discussionmentioning

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

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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...

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Section: Discussionmentioning

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

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“…A 1 receptors mediated mobilization of Ca 2ϩ in human bronchial smooth muscle cells (Ethier and Madison, 2006). Other studies suggested that xanthine-resistant A 3 receptors dominated (Thorne et al, 1996). Experiments on rabbit airway smooth muscle suggested that adenosine causes relaxation via an A 2 receptor that releases nitric oxide from the epithelium (Ali et al, 1997).…”

Section: Airway Smooth Musclementioning

confidence: 99%

Purinergic Signaling in the Airways

Burnstock

Brouns²,

Adriaensen³

et al. 2012

Pharmacol Rev

173

158

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“…Both in vitro [17,85] and in vivo [86,87] studies have established that activation of A 3 receptors results in mast-cell degranulation and/or enhancement of mast degranulation in response to allergen in a variety of rodent species. However, A 3 -receptor protein was not found in association with human lung mast cells [18], thus questioning its relevance in the mechanism of adenosine-induced bronchoconstriction in humans.…”

Section: Adenosine a 3 Receptorsmentioning

confidence: 99%

Adenosine-receptor subtypes: their relevance to adenosine-mediated responses in asthma and chronic obstructive pulmonary disease

2002

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Adenosine-receptor subtypes: their relevance to adenosine-mediated responses in asthma and chronic obstructive pulmonary disease. R. Polosa. #ERS Journals Ltd 2002. ABSTRACT: Adenosine administration by inhalation elicits concentration-related bronchoconstriction in subjects with asthma and chronic obstructive pulmonary disease (COPD). The mechanisms of adenosine-induced bronchoconstriction appear to involve a selective interaction with activated mast cells with subsequent release of preformed and newly-formed mediators. Further evidence linking adenosine signalling to asthma and COPD comes from the finding that many cell types that play important roles in the exacerbation of these conditions express adenosine receptors and demonstrate relevant effects through stimulation of these receptors.Therefore, blockade of these receptors may be a valuable approach to the treatment of asthma and chronic obstructive pulmonary disease. Promising adenosine-receptor targets for novel therapeutics of asthma and chronic obstructive pulmonary disease have recently been identified in a number of inflammatory cell types, including mast cells, eosinophils, lymphocytes, neutrophils, and macrophages. The recent characterisation of the A 2B receptors indicates the human lung mast cell as one of the most strategic cellular targets. Eur Respir J 2002; 20: 488-496.

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Analysis of the bronchoconstrictor responses to adenosine receptor agonists in sensitized guinea-pig lungs and trachea

Cited by 30 publications

References 23 publications

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

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

Purinergic Signaling in the Airways

Adenosine-receptor subtypes: their relevance to adenosine-mediated responses in asthma and chronic obstructive pulmonary disease

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