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Adenosine receptor subtypes in airways responses of sensitized guinea-pigs to inhaled ovalbumin

Smith, Nicola and Broadley, Kenneth John 2010. Adenosine receptor subtypes in airways responses of sensitized guinea-pigs to inhaled ovalbumin. Pulmonary Pharmacology and Therapeutics 23 (4) , pp. 355-364. 10.1016/j.pupt.2010.03.010

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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 ovalbum in 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 mg/ml) of sensitized, conscious guinea-pigs were recorded by whole body plethysmography following administration of selective adenosine recepto rantagonists.Airway reactivity to inhaled histamine(1mM)and inflam- matory cell influx in bronchoalveolar lavage fluid were also determined 24h 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 receptorantagonist)inhibited the airways hyperreactivity and cellular influx and enhanced the EAR.MRS1220(A3 receptorantagonist) inhibited the airways hyperreactivity and cellular influx without affecting EAR and LAR.Dexamethasone inhibited the ovalbumin-induced late asthmaticresponses,airways hyperreactivity and cellular influx. The blockade o fairway 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Subjects: R Medicine > RM Therapeutics. Pharmacology
R Medicine > RS Pharmacy and materia medica
Uncontrolled Keywords: Ovalbumin ; Sensitized guinea-pigs ; Inflammatory cell influx ; EAR ; LAR ; Airways hyperreactivity ; Adenosine receptors
Publisher: Elsevier
ISSN: 1094-5539
Last Modified: 04 Jun 2017 03:01
URI: http://orca.cf.ac.uk/id/eprint/15429

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