Specific antagonism of adenosine-induced bronchoconstriction in asthma by oral theophylline.
The airway response to increasing concentrations of inhaled-adenosine and histamine after oral theophylline or matched placebo was studied in nine asthmatic subjects. Changes in airway calibre were followed as sGaw and FEV1 and concentration-response curves constructed. Inhaled adenosine caused concentration-related bronchoconstriction and was four-five times less potent than inhaled histamine. Theophylline, which achieved a mean plasma level of 15.9 and 16.6 micrograms/ml on the histamine and adenosine study days respectively, caused significant increases in FEV1 (17%) and sGaw (41-53%) whereas placebo had no effect. Theophylline also protected the airways against histamine-and adenosine-induced bronchoconstriction. However theophylline had a greater protective effect against adenosine (concentration-ratio 17.4 for FEV1 and 12.8 for sGaw) than against histamine (concentration ratio 5.6 for FEV1 and 5.4 for sGaw (P less than 0.05]. At therapeutic concentrations theophylline is a specific antagonist of the airway effects of adenosine in addition to being a bronchodilator and a functional antagonist.
D000241:Adenosine / Q000037:antagonists & inhibitors*; D000328:Adult; D000403:Airway Resistance / Q000187:drug effects; D001249:Asthma / Q000503:physiopathology*; D001980:Bronchi / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000494:pharmacology; D005260:Female; D005541:Forced Expiratory Volume; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D008297:Male; D011897:Random Allocation; D013806:Theophylline / Q000097:blood / Q000494:pharmacology*
D001993:Bronchodilator Agents; D006632:Histamine; D013806:Theophylline; D000241:Adenosine