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

European Journal of Pharmacology
A J Schreurs, F P Nijkamp


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 beta-adrenoceptor function. A [3H]dihydroalprenolol binding assay was used to determine the number of beta-adrenoceptors (Bmax) following H. influenzae vaccination. The Bmax 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 beta-adrenoceptors was evaluated in our model. Pretreatment with Ro4-4602, an inhibitor of dopa-decarboxylase, increased the number of beta-adrenoceptors and prevented the H. influenzae-induced loss of beta-adrenoceptors. On the other hand repeated doses of the antidepressant desipramine mimicked the effect of H. influenzae vaccination i.e. a loss of beta-adrenoceptors. Desipramine and H. influenzae vaccination were not synergistic in their effects. The effects of H. in...Continue Reading


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