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Adenosine receptor subtypes in the airways responses to 5′‐adenosine monophosphate inhalation of sensitized guinea‐pigs
Author(s) -
Smith N.,
Broadley K. J.
Publication year - 2008
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/j.1365-2222.2008.03034.x
Subject(s) - bronchoconstriction , adenosine , inhalation , adenosine monophosphate , adenosine receptor , histamine , medicine , endocrinology , receptor , guinea pig , bronchoalveolar lavage , cyclic adenosine monophosphate , pharmacology , agonist , asthma , anesthesia , lung
Summary Background Endogenous adenosine levels are raised in the lungs during asthma attacks. 5′‐adenosine monophosphate (5′‐AMP) inhalation in asthmatics causes bronchoconstriction and in sensitized guinea‐pigs induces early (EAR) and late asthmatic responses (LAR), airway hyper‐reactivity (AHR) and inflammatory cell recruitment to the lungs. Objective The aim of this study was to investigate the roles of A 1 , A 2A , A 2B and A 3 adenosine receptors in these responses to inhaled 5′‐AMP in sensitized guinea‐pigs. Comparisons were made with the effect of dexamethasone treatment on 5′‐AMP‐induced responses. Methods Functional airways responses to inhaled 5′‐AMP (3 and 300 m m ) of actively sensitized, conscious guinea‐pigs were determined by whole‐body plethysmography following administration of selective adenosine receptor antagonists or their vehicles. AHR to inhaled histamine (1 m m ) and inflammatory cell influx in bronchoalveolar lavage fluid were determined. Results 5′‐AMP at 3 m m caused an immediate bronchoconstriction (EAR), whereas 300 m m caused bronchodilatation. Both responses were followed at 6 h by a LAR, together with inflammatory cell influx and AHR to histamine. The A 2A receptor antagonist, ZM241385, further enhanced cell influx after 5′‐AMP inhalation (3 and 300 m m ), and blocked the immediate bronchodilator response to 300 m m 5′‐AMP, exposing an EAR. The A 2B receptor antagonist, MRS1706 (in the presence of ZM241385), inhibited the LAR, AHR and cell influx, following inhalation of 5′‐AMP (300 m m ). The A 3 receptor antagonist, MRS1220, inhibited 5′‐AMP‐induced inflammatory cell influx. The A 1 receptor antagonist, DPCPX (in the presence of ZM241385), inhibited the EAR following 5′‐AMP inhalation (300 m m ). Dexamethasone inhibited the LAR, AHR and cell influx following inhalation of 5′‐AMP (300 m m ). Conclusion All four adenosine receptor subtypes play various roles in the airways responses to inhaled 5′‐AMP in sensitized guinea‐pigs.