A Comparison of <i>β</i>-Adrenergic Receptors and <i>In Vitro</i> Relaxant Responses to Isoproterenol in Asthmatic Airway Smooth Muscle

In previous reports, we have documented decreased in vitro airway smooth muscle responses to isoproterenol (ISO) in fresh postmortem trachea and bronchus from subjects with fatal asthma. One hypothesis to explain this finding is a decrease in β-adrenergic receptor (βAR) numbers on airway smooth muscle. We have now examined the autoradiographic distribution and density of βAR using [125I]iodocyanopindolol on sections of airway smooth muscle adjacent to those studied functionally. The results have been compared with "normal" trachea and bronchi obtained from persons dying suddenly of nonpulmonary causes. In both trachea and bronchi, there was a 2.8-fold and 2.5-fold increase in specific grain counts, respectively, over smooth muscle from asthmatic airways (n = 6) compared with that determined in normal airways (n = 4, P < 0.01, unpaired t test). The affinity of the βAR for the agonist ISO, as determined by competitive binding experiments with increasing concentrations of (−)-ISO on tissue sections, was increased in asthmatic bronchi (IC50 = 80 ± 13 nM; n = 3) compared with normal bronchi (IC50 = 562 ± 144 nM; n = 4, P < 0.05). We conclude that βAR-mediated relaxant abnormalities in airway smooth muscle in fatal asthma cannot be explained by a decrease in receptor number and, surprisingly, βAR expression is increased.