Concomitant glucocorticoid treatment prevents the development of beta-adrenoceptor desensitization in the guinea pig lung.

The aim of the present study was to investigate, whether concomitant administration of the synthetic glucocorticoid betamethasone (BM), theophylline (THEO), or the muscarinic antagonist ipratropium bromide (IPRA) could influence the desensitization-associated decrease of beta-adrenoceptors in the guinea pig lung during prolonged in vivo treatment with the beta 2-agonist terbutaline (TER). The animals were sacrificed 20 hrs after the last drug dosage and the lung membrane homogenates were prepared for 3H-dihydroalprenolol (3H-DHA) binding in vitro. Treatment with TER 200 micrograms/kg subcutaneously twice a day for five days decreased by 22% the maximum number of binding sites (Bmax) at saturation in comparison with the saline-treated controls. Concomitant administration of BM 2 mg/kg intraperitoneally abolished this effect of TER, whereas THEO 20 mg/kg or IPRA 5 micrograms/kg failed to modify it. None of the in vivo treatments affected the binding affinity of 3H-DHA. In vitro, TER inhibited in a concentration-dependent manner 3H-DHA binding to the lung membranes of untreated guinea pigs. At high concentrations IPRA, but not THEO or BM, showed some binding to the beta-receptors as well. Thus, it is concluded that glucocorticoids may prevent beta-adrenoceptor desensitization in the lungs via an indirect mechanism, e.g. inhibition of phospholipase A2 enzyme.