Hyperresponsiveness to adenosine in sensitized Wistar rats over-expressing A₁ receptor
2012
Alfieri, Alessio | Parisi, Antonio | Maione, Francesco | Grassia, Gianluca | Morello, Silvana | Ialenti, Armando | Mascolo, Nicola | Cicala, Carla
Airway hyperreactivity is characterized by increased responsiveness to bronchoconstrictor stimuli and it is hallmark of asthma. Adenosine is an ubiquitous signaling nucleoside resulting from ATP catabolism, whose extracellular levels increase following cellular damage or stress. Adenosine plays a role in asthma; asthmatics, but not normal subjects, present bronchoconstriction following inhalation of adenosine or of its precursor, adenosine-5′-monophosphate, most likely via adenosine A₂B receptor on mast cells. However, the mechanism underling the increased airway smooth muscle sensitivity to adenosine in asthmatics remains to be elucidated. Early experimental studies suggested the involvement of A₁ receptor; this hypothesis has been confirmed by more recent studies on guinea pigs and is corroborated by the finding of an increased adenosine A₁ expression on asthmatic bronchial tissues. Brown Norway rats, the strain usually used to assess asthma models, develop hyperresponsiveness to adenosine 3h following allergen challenge, but not 24h thereafter, without involvement of A₁ receptor. Here, we investigated the role of adenosine A₁ receptor in sensitized Wistar rats showing airway hyperresponsiveness 24h following allergen challenge. We found that on bronchi of sensitized Wistar rats challenged with allergen there is an increased adenosine A₁ receptor expression on smooth muscle that is responsible for hyperresponsiveness to adenosine and ovalbumin.
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