Viral Pneumonia Attenuates Adenylate Cyclase But Not Beta-Adrenergic Receptors in Murine Lung

Abstract

Respiratory infections provoke increased airway reactivity in both asthmatic and otherwise healthy subjects in part through impaired beta-adrenergic relaxation of bronchial and tracheal muscle. The precise mechanism remains obscure, but some studies report a decrease in the number of beta-adrenergic receptors. The present study was designed to assess the effect of viral respiratory infection with influenza A on lung beta-adrenergic receptors and adenylate cyclase activation in mice under two separate protocols. First, to determine whether changes are due to a local or systemic effect, we compared mice with influenza infections limited to the upper respiratory tract to mice with infection of the total respiratory tract. Four days after upper respiratory tract infection there were no changes in either isoproterenol- or NaF-stimulated adenylate cyclase activity. In contrast, there was an 82% decrease in isoproterenol- and a 25% decrease in NaF-stimulated adenylate cyclase activity on the fourth day after total respiratory tract infection. There were no changes in beta-adrenergic receptors or receptor coupling to adenylate cyclase with either type of infection. Our second protocol compared acutely infected mice to postrecovery mice. Twelve days after infection the virus was no longer present in the lungs, and adenylate cyclase activity was restored to normal. These data suggest that viral respiratory infection may impair airway function through attenuation of receptor and postreceptor activation of adenylate cyclase activity.