Bronchodilator drug efficacy via cyclic AMP.

Abstract

Cyclic adenosine 3', 5'-monophosphosphate (cyclic AMP) as measured by radioimmunoassay is found in diced rat lung in an amount approximating one picomole per milligram of wet weight lung tissue. Incubation of rat lung with adrenaline, a beta adrenergic agent, produced a rapid increase in cyclic AMP, 100% increase at 15 seconds and 340% at 2 minutes. Isoprenaline was more stimulatory than adrenaline; noradrenaline was less stimulatory, and ephedrine produced a negligible effect. The methylxanthines, caffeine and theophylline, produced an increase in cyclic AMP concentration. Of these, caffeine was more potent, and synergism with adrenaline was demonstrated. The beta adrenergic blocking agent, propranolol, completely inhibited the expected rise in cyclic AMP secondary to adrenaline stimulation. In contrast, the alpha blocker, phentolamine, produced no effect. This animal model offers evidence that adrenergic agents and methylxanthines act to increase cyclic AMP in lung tissue. It is likely that many of the beneficial effects of these drugs in pulmonary patients occur through similar changes and modulation of the cyclic AMP system.