Haemophilus influenzae induced loss of lung β-adrenoceptor binding sites and modulation by changes in peripheral catecholaminergic input

Abstract

Vaccination of guinea pigs with killed suspensions of Haemophilus influenzae, a bacterium often found in the deeper respiratory airways of asthmatic bronchitics, results in a number of effects suggesting an impairment of β-adrenoceptor function. A [ 3H]dihydroalprenolol binding assay was used to determine the number of β-adrenoceptors (B max) following H. influenzae vaccination. The B max declined significantly by 29% from 1240±80 to 880±70 fmol/mg protein, while the binding affinity of the sites was not changed. Specific binding in the presence of 1.8 nM [ 3H]DHA to tracheal longitudinal smooth muscle was also significantly lower in H. influenzae-vaccinated animals as compared to controls. Furthermore modulation of peripheral sympathetic input to lung β-adrenoceptors was evaluated in our model. Pretreatment with Ro4-4602, an inhibitor of dopa-decarboxylase, increased the number of β-adrenoceptors and prevented the H. influenzae-induced loss of β-adrenoceptors. On the other hand repeated doses of the antidepressant desipramine mimicked the effect of H. influenzae vaccination i.e. a loss of β-adrenoceptors. Desipramine and H. influenzae vaccination were not synergistic in their effects. The effects of H. influenzae and modulation of catecholaminergic input on guinea pig lung β-adrenoceptors were compared with tracheal strip relaxation by isoproterenol, following similar treatments assessed in a superfusion model. Changes in lung β-adrenoceptor number were almost identical with changes in tracheal strip relaxation. These results suggest that compensatory regulation adapts the number of respiratory β-adrenoceptors to changes in sympathetic input. A similar mechanism may underlie the loss of β-adrenoceptors following H. influenzae vaccination.