Adenosine-induced bronchoconstriction in the guinea-pig isolated lung: Interaction with theophylline and enprofylline

Abstract

Effects of purine nucleosides and asthma mediators on airway tone have been examined in the guinea-pig isolated perfused lung preparation. Acetylcholine (10 pmol-0.3 nmol), histamine (1-10 nmol), adenosine (10 nmol-0.3 mumol), ATP (10 nmol-0.3 mumol) and inosine (10 mumol-0.1 mmol) all produced a dose dependent increase in lung resistance (RL) and a decrease in dynamic compliance (CDYN). ATP was equipotent with adenosine whereas inosine was about 500 times less potent. The adenosine-induced bronchoconstriction was affected neither by disodium cromoglycate (150 microM) nor by the histamine H1-receptor antagonist, mepyramine (1 microM) suggesting that histamine is not involved in this response. Furthermore, it was studied whether the xanthines theophylline and enprofylline specifically interacted with the adenosine induced bronchoconstriction. Theophylline significantly (P less than 0.01-0.001) and concentration dependently prevented both acetylcholine and adenosine-induced increase in RL. The response to 0.1 nmol acetylcholine was reduced by 32.8 +/- 8.4% (mean +/- SEM) and 58.1 +/- 4.0%, respectively, by 75 and 150 microM theophylline. Theophylline, 75 and 150 microM, also inhibited the increase in RL caused by 0.1 mumol of adenosine by 61.4 +/- 9.6% and 83.4 +/- 5.2%, respectively. Theophylline, was significantly (P less than 0.05-0.01) more potent in preventing the RL increase produced by adenosine than that by acetylcholine. Enprofylline, 30 microM, equally well as 75 microM theophylline reduced the acetylcholine-induced bronchoconstriction by 41.8 +/- 7.6% (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)