title: Relationships between adenosine, cyclic nucleotides, and xanthines in asthma.
abstract: Methylxanthines have been used for the treatment of asthma for more than 60 years, but their mechanism of action is poorly understood. Their ability to inhibit cyclic adenosine monophosphate phosphodiesterase has attracted much attention. However, this is clearly demonstrable only in high doses and is more likely to be related to toxicity. An alternative mechanism is antagonism of adenosine receptors in the lung. Adenosine has been shown to be released in asthma and cause bronchoconstriction in patients with asthma. Its effects are selectively inhibited by concentrations of theophylline that do not block histamine-induced bronchoconstriction. Neither phosphodiesterase inhibition nor adenosine receptor antagonism explains the action of enprofylline in asthma. Consequently, additional actions of methylxanthines are likely to contribute to their beneficial effects. They may include adrenaline release from the adrenal medulla, an effect on cell calcium distribution, inhibition of the generation of contractile prostaglandins, and an improvement of diaphragmatic contractility.
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000241:Adenosine / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism; D001980:Bronchi / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism; D006801:Humans; D014970:Xanthines / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D002395:Catecholamines; D014970:Xanthines; C008514:methylxanthine; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000241:Adenosine