Adenosine receptor subtypes in airways responses of sensitized guinea-pigs to inhaled ovalbumin |
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| Authors: | Nicola Smith Kenneth J. Broadley |
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| Affiliation: | 1. Pulmonary Cell Research, Department of Biomedicine, University Hospital Basel, Switzerland;2. Pulmonology, Department of Internal medicine, University Hospital Basel, Switzerland;3. Department of Thoracic Surgery, University Hospital Basel, CH-4031 Basel, Switzerland;3. Department of Molecular Physiology and Biophysics, Houston, Texas 77030;4. Graduate Program in Molecular Physiology and Biophysics, Houston, Texas 77030;5. Interdepartmental Graduate Program in Translational Biology and Molecular Medicine, Houston, Texas 77030;6. Asthma Clinical Research Center, Houston, Texas 77030;8. Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas 77030;12. Peptides International, Louisville, Kentucky 40299;1. Division of Cellular Pharmacology, Department of Pharmacology, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Três de Maio, 100, 04044-020 São Paulo, SP, Brazil;2. Department of Biochemistry, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil;1. Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil;2. Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil;3. Post Graduate Program in Biophotonics Applied to Health Sciences, Nove de Julho University, São Paulo, Brazil;4. Hospital das Clinicas of the Faculty of Medical Sciences, University of São Paulo, Brazil;5. Biomedical Engineering Laboratory, Department of Telecommunication and Control Engineering, School of Engineering, University of São Paulo, Brazil |
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| Abstract: | Endogenous adenosine is released in asthmatic patients’ lungs by inhaled allergen, however, its exact role in asthmatic responses or the receptors mediating these responses has not been determined. Our hypothesis was that adenosine released during allergen challenge contributes to the airways responses to inhaled allergen. The effects of selective antagonists of the four adenosine receptor subtypes were investigated on the airways responses of sensitized guinea-pigs to inhaled ovalbumin to ascertain the role of adenosine in these allergen responses, and compared with a corticosteroid, dexamethasone.Early (EAR) and late asthmatic responses (LAR) to inhaled ovalbumin (10 μg/ml) of sensitized, conscious guinea-pigs were recorded by whole body plethysmography following administration of selective adenosine receptor antagonists. Airway reactivity to inhaled histamine (1 mM) and inflammatory cell influx in bronchoalveolar lavage fluid were also determined 24 h after ovalbumin challenge.ZM241385 (A2A receptor antagonist) did not affect these responses, whereas DPCPX (A1 receptor antagonist) exerted a small inhibition only of the LAR. MRS1706 (A2B receptor antagonist) inhibited the airways hyperreactivity and cellular influx and enhanced the EAR. MRS1220 (A3 receptor antagonist) inhibited the airways hyperreactivity and cellular influx without affecting EAR and LAR. Dexamethasone inhibited the ovalbumin-induced late asthmatic responses, airways hyperreactivity and cellular influx.The blockade of airway hyperreactivity and inflammatory cell influx by A2B and A3 receptor antagonists suggests that endogenous adenosine is released by inhaled allergen and these responses are mediated via A2B and A3 receptors in guinea-pigs. The adenosine released by allergen inhalation does not, however, appear to be involved in the EAR, but it may contribute to the LAR via A1 receptors. |
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