Depressed cyclic AMP levels in airway smooth muscle from asthmatic dogs

Abstract

Mongrel dogs were tested by intradermal injection and tracheobronchial aerosol challenge with Ascaris suum antigen extract. All dogs were skin-test positive but could be segregated on the basis of airways resistance measurements, into asthmatic (bronchoreactive) and nonasthmatic (non-bronchoreactive) groups. Tracheal rings from these dogs were used to measure the abilities of the .beta.-adrenergic agonist, isoproterenol was measured to relax tracheal smooth muscle contracted by methacholine and to cause cyclic[c]AMP accumulation in the presence and absence of methacholine. The magnitude of relaxation induced by any concentration of isoproterenol was always less in the smooth muscle from asthmatic dogs. In the same tissues the cAMP concentrations after in vitro equilibration, but prior to isoproterenol addition, were significantly less in the asthmatic than nonasthmatic samples. The cAMP accumulation due to isoproterenol was similar in both groups for every dose of isoproterenol so that the initial difference between groups in cAMP concentration was maintained in an additive fashion over the entire dose-response curve. Total protein content of trachealis muscles from both groups of dogs was the same. .beta.-Adrenergically sensitive adenylate cyclase is apparently not impaired in tracheal smooth muscle from asthmatic dogs; the basal concentration of cAMP is depressed in asthmatic airway smooth muscle. This difference is maintained throughout the isoproterenol dose-response curve. The depressed intracellular cAMP concentrations may be related to the decreased relaxation induced by isoproterenol in the asthmatic tracheal smooth muscle.