Haemophilus influenzae induced loss of lung beta-adrenoceptor binding sites and modulation by changes in peripheral catecholaminergic input.
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. influenzae and modulation of catecholaminergic input on guinea pig lung beta-adrenoceptors were compared with tracheal strip relaxation by isoproterenol, following similar treatments assessed in a superfusion model. Changes in lung beta-adrenoceptor number were almost identical with changes in tracheal strip relaxation. These results suggest that compensatory regulation adapts the number of respiratory beta-adrenoceptors to changes in sympathetic input. A similar mechanism may underlie the loss of beta-adrenoceptors following H. influenzae vaccination.
D000818:Animals; D001428:Bacterial Vaccines / Q000494:pharmacology*; D002395:Catecholamines / Q000378:metabolism*; D006168:Guinea Pigs; D006193:Haemophilus influenzae / Q000276:immunology*; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism*; D009126:Muscle Relaxation; D009130:Muscle, Smooth / Q000187:drug effects; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D014132:Trachea / Q000187:drug effects
D001428:Bacterial Vaccines; D002395:Catecholamines; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta