Mechanism of airway hyperresponsiveness to adenosine induced by allergen challenge in actively sensitized Brown Norway rats

1 We have explored the role of allergen sensitization and challenge in defi ning the response of the airways of the Brown Norway (BN) rat to adenosine. 2 In naive animals or in rats sensitized to ovalbumin (OA) adenosine induce d only weak bronchoconstrictor responses. Challenge of sensitized animals w ith OA induced a marked airway hyperresponsiveness to adenosine which was n ot seen with methacholine or bradykinin. 3 The augmented bronchoconstrictor response to adenosine was not affected b y acute bivagotomy or atropine nor mimicked by an i.v, injection of capsaic in. It was, however, blocked selectively by disodium cromoglycate methyserg ide or ketanserin and reduced in animals treated sub-chronically with compo und 48/80. 4 The augmented response to adenosine was associated with increases in the plasma concentrations of both histamine and 5-hydroxytryptamine (5-HT), whi ch were attenuated by pretreatment with disodium cromoglycate, and degranul ation of mast cells in the lung. 5 Parenchymal strips from lungs removed from sensitized rats challenged wit h OA gave augmented bronchoconstrictor responses to adenosine relative to s trips from sensitized animals challenged with saline. Responses were inhibi ted by methysergide and disodium cromoglycate. 6 These data demonstrate a marked augmentation of the bronchoconstrictor re sponse to adenosine in actively sensitized BN rats challenged with OA. The augmented response is primarily a consequence of mast cell activation, lead ing to the release of 5-HT, which in turn induces bronchoconstriction. Our data further suggest the involvement of a discrete lung-based population of mast cells containing and releasing mainly 5-HT and brought into play by p rior exposure to allergen.