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Early- and late-phase bronchoconstriction, airway hyper-reactivity and cell influx into the lungs, after 5′-adenosine monophosphate inhalation: comparison with ovalbumin


Dr F. J. Johnson, Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3XF, UK.


Background Antigen inhalation in atopic asthmatic patients results in an early asthmatic response (EAR), accompanied by a late asthmatic response (LAR) in 60% of patients. Inhaled 5′-adenosine monophosphate (5′-AMP) causes immediate bronchoconstriction in asthmatics but not in normal subjects.

Objectives The aims of this study were to investigate whether 5′-AMP can produce a LAR, airway hyper-reactivity (AHR) and cell influx to the lungs, in a sensitized guinea-pig model of asthma, and to compare with the profile of activity after ovalbumin (OVA) inhalation.

Methods Airway responses to inhaled OVA (10 μg/mL) and 5′-AMP (3 and 300 mm) of actively sensitized, conscious guinea-pigs were determined by whole body plethysmography as the change in specific airway conductance (sGaw). Inhaled histamine (1 mm) was used to investigate AHR, and cell influx was determined by bronchoalveolar lavage (BAL).

Results Exposure to OVA revealed an EAR, and LAR at 6 h post-challenge. AHR to histamine occurred 24 h after challenge together with a significant increase in total and differential (eosinophils and macrophages) cell counts. Low dose 5′-AMP (3 mm) produced an EAR, LAR at 6 h after challenge, and AHR to histamine 12 h post-challenge. No AHR occurred 24 h after inhalation. Total and macrophage cell counts were increased significantly 6, 12 and 24 h after exposure. Bronchodilatation followed high dose 5′-AMP (300 mm), followed by a LAR at 6 h. AHR to histamine occurred 12 h after challenge, but not at 24 h. A significant increase in total and differential (eosinophils and macrophages) cell counts occurred 6, 12 and 24 h post-exposure. No changes were observed in non-sensitized guinea-pigs.

Conclusion OVA challenge revealed an EAR, LAR, cell influx and AHR in a guinea-pig model of asthma. This study demonstrated for the first time that a LAR and AHR to histamine can be revealed following 5′-AMP inhalation, in sensitized but not unsensitized guinea-pigs. Cell influx at 6, 12 and 24 h post-challenge suggests that it may be associated with the LAR and AHR.

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