Active sensitisation modifies β-adrenoceptor reactivity in guinea-pig trachea

Abstract

The occurrence of beta-adrenoceptor desensitisation in clinical experience, after long term therapy with specific beta 2-agonists, is still an open question, even if this phenomenon is easily observed in different experimental models. Since the majority of these experiments have been performed in normal animals, we investigated the possible occurrence of beta-adrenoceptor desensitisation in the ovalbumin actively sensitised guinea-pig model of experimental asthma. The isoproterenol concentration-response curves performed in pilocarpine contracted guinea-pig trachea in vitro were shifted to the right by the beta-adrenoceptor desensitisation procedure, which was achieved by the in vitro administration of isoproterenol (10(-5) M x 2 times x 20 min each) both in normal and ovalbumin sensitised tissues. The same desensitisation procedure markedly affected epinephrine-relaxing capacity in both normal and ovalbumin actively sensitised guinea-pig tracheae. However, the ovalbumin sensitised tissue seemed to be more sensitive than normal to the specific beta 2-agonist procaterol; in parallel the beta 2-mediated relaxation was more impaired by isoproterenol-induced beta-adrenoceptor down regulation in ovalbumin sensitised trachea when compared to normal. Similar results have been obtained using salbutamol as the beta 2-adrenoceptor desensitising agent. The changes in beta-adrenoceptor reactivity between normal and ovalbumin sensitised guinea-pig tracheae seemed to depend on the active sensitisation process. No difference in the degree of beta-adrenoceptor down regulation was observed in passively ovalbumin sensitised guinea-pig trachea as compared to normal. These data suggest that, in this model of experimental asthma, beta-adrenoceptor reactivity is in some way modified and that this phenomenon might contribute to the genesis of asthma.