Adenosine-induced bronchoconstriction in asthma. Antagonism by inhaled theophylline.
Inhaled adenosine causes bronchoconstriction in asthmatic patients. Antagonism of the bronchoconstrictor effect of endogenous adenosine has been proposed as a possible mechanism of action of theophylline in asthma. To directly investigate this, we have compared the airway responses to inhaled adenosine and histamine, with and without the prior administration of inhaled theophylline in 8 allergic asthmatic subjects. Airway response was measured both as forced expiratory volume in one second (FEV1) and as specific airway conductance (SGaw). Inhaled adenosine was less potent than histamine in producing bronchoconstriction, with geometric mean concentrations required to produce a 20% fall of FEV1 (PCf20) and a 40% fall of SGaw (PCs40) being 0.27 and 0.25 mg/ml for adenosine and 0.10 and 0.09 mg/ml for histamine. In a total nebulized dose of 37.5 mg, inhaled theophylline was a weak bronchodilator that caused maximal increases in FEV1 of 2 +/- 2% (mean +/- SE, p less than 0.05) and in SGaw of 8 +/- 4% (p greater than 0.05). However, theophylline significantly inhibited adenosine-induced bronchoconstriction, increasing the PCf20 and PCs40 values for adenosine to 1.66 (p less than 0.001) and 2.34 (p less than 0.005) mg/ml, respectively. Inhibition of histamine-induced bronchoconstriction was less marked, with PCf20 and PCs40 values of 0.19 (p greater than 0.05) and 0.21 (p less than 0.05) mg/ml. Thus, adenosine is a bronchoconstrictor in asthma whose effects are preferentially antagonized by concentrations of theophylline that cause little change in baseline airway caliber.(ABSTRACT TRUNCATED AT 250 WORDS)
D000241:Adenosine / Q000494:pharmacology*; D000328:Adult; D000403:Airway Resistance / Q000187:drug effects; D001249:Asthma / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D005260:Female; D005541:Forced Expiratory Volume; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D008297:Male; D013806:Theophylline / Q000494:pharmacology*
D006632:Histamine; D013806:Theophylline; D000241:Adenosine