Journal of Applied Physiology, Vol 47, Issue 2 330-336, Copyright © 1979 by American Physiological Society
Mechanisms of airway smooth muscle response to isoproterenol and theophylline
D. E. Niewoehner, H. Campe, S. Duane, T. McGowan and M. R. Montgomery
Airway smooth muscle preparations from various sites and species exhibit a
range of sensitivities to the same beta-adrenergic agonist. This
variability has been attributed to beta-receptor function but the exact
mechanism determining the response has not been identified. After first
inducing contraction with acetylcholine, we measured isoproterenol and
theophylline relaxation responses in five separate airway smooth muscle
preparations in vitro. The order of sensitivity was identical for both
drugs: guinea pig trachea greater than dog lung strip greater than dog
bronchiole greater than rat trachea greater than dog trachea. Because of
evidence that both drugs act by increasing adenosine 3',5'-cyclic
monophosphate (cAMP) concentrations, we utilized a kinetic model of cAMP
metabolism to investigate the possibility that the identical order of
sensitivity to both drugs could be explained by a common mechanism.
Relaxation responses to both drugs are in accord with known kinetic data.
Small differences in the velocity constants of enzymes affecting cAMP
metabolism or differences in the relaxation response to the same
concentrations of cAMP can fully explain the variable muscle responses to
both drugs.
