Effect of albuterol and terbutaline, synthetic beta adrenergic stimulants, on the cyclic 3',5'-adenosine monophosphate system in smooth muscle.

The effect of albuterol and terbutaline on the cyclic 3',5'-adenosine monophosphate (cAMP) system was studied in rat uterus, aorta and myocardium and in dog bronchus, and was compared to that of isoproterenol in order to determine whether the tissue specificity observed in their functional effects is reflected in their effect on the cAMP system. Tissue specimens were either homogenized in Tris buffer for enzyme activity measurements or incubated in Krebs-Ringer-bicarbonate medium with the test drugs. Both albuterol and terbutaline produce an increase in cAMP content in the tissues due to a direct effect on adenylate cyclase. This effect can be potentiated by a phosphodiesterase inhibitor and antagonized by a beta adrenergic blocking compound. The cAMP response to each beta adrenergic agonist differs in the tissues examined: in uterus and aorta where the maximal effects are idenitcal, the ED50 values may reflect differences in affinity which may account for the different cAMP response to the compounds at the lower concentrations. In bronchus and myocardium, both the maximum effect and ED50 values of the compounds are different. Albuterol and terbutaline increases cAMP content in bronchus significantly and have only a small effect on cAMP cont in myocardium, whereas isoproterenol increases cAMP level significantly in both tissues. The results indicate that the tissue specificity of albuterol and terbutaline may have its origin at the level of the cAMP system.