Adenosine-induced bronchoconstriction in asthma: role of mast cell-mediator release.
Adenosine, when it is administered by inhalation to asthmatic subjects, is a potent bronchoconstrictor, although its mechanism of action is not known. Since adenosine has been demonstrated to potentiate IgE-dependent mediator release from mast cells, we have investigated the possible relationship between adenosine-induced bronchoconstriction and release of mast cell mediators in 14 asthmatic subjects. In the first study the effect of the putative mast cell-stabilizing drug cromolyn sodium (SCG) was observed on the dose-related changes in SGaw and FEV1 produced by inhaled adenosine and histamine in seven subjects. Inhaled SCG (20 mg) had no effect on the airway responses to histamine. In contrast SCG significantly protected against adenosine-induced bronchoconstriction in four of the seven subjects as reflected by a decrease in the airway response to the highest concentrations of adenosine, from 65 +/- 8% to 12 +/- 3% (mean +/- SEM) for SGaw and 31 +/- 7% to 8 +/- 3% for FEV1. Those three subjects whose adenosine response was unaffected by SCG had received regular SCG until 12 hr before the studies. In a separate study on eight subjects, a single inhalation of adenosine, causing a maximum 61 +/- 4% fall in SGaw at 10 min, had no significant effect on circulating levels of histamine, neutrophil chemotactic factor, or cyclic AMP. Together these two studies suggest that bronchoconstriction produced by adenosine is not a consequence of enhanced mast cell-mediator release and that the inhibitory effects of SCG occur by a mechanism other than through mast cell stabilization.
Cushley
M J
MJ
Holgate
S T
ST
D000241:Adenosine; D000328:Adult; D001249:Asthma / Q000097:blood / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D001986:Bronchial Spasm / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D002630:Chemotactic Factors / Q000097:blood; D004205:Cromolyn Sodium / Q000494:pharmacology; D000242:Cyclic AMP / Q000097:blood; D005260:Female; D005541:Forced Expiratory Volume; D006632:Histamine / Q000097:blood; D006801:Humans; D016209:Interleukin-8; D008297:Male; D008407:Mast Cells / Q000378:metabolism*; D008875:Middle Aged
D002630:Chemotactic Factors; D016209:Interleukin-8; D006632:Histamine; D000242:Cyclic AMP; D000241:Adenosine; D004205:Cromolyn Sodium