GLUCOCORTICOID MODULATION OF MUSCARINIC AND BETA-ADRENERGIC RECEPTORSIN GUINEA-PIG LUNG

We investigated the effect of the in vivo treatment of guinea pigs wit h methylprednisolone, 10 mg/kg daily, on lung muscarinic and beta-adre nergic receptors. Receptor densities were assessed by saturation exper iments of tritiated N-methylscopolamine and dihydroalprenolol binding to lung membranes. After 3 h of treatment, methylprednisolone induced a decrease of 19.2% (P < 0.05) of muscarinic receptors but was without effect on beta-adrenergic receptor density. After 24 h, an increase o f 39.7% (P < 0.01) and 16.9% (P < 0.05) was observed for muscarinic an d beta-adrenergic receptors, respectively. For muscarinic receptors, t his increase reached 53.4% (P < 0.01) within 48 h and stayed at this l evel until 96 h. The increase of beta-adrenergic receptors was maximal (24.9%) after 72 h and returned to the control value after 96 h. The dissociation constant (K-d) values of both ligands were not affected b y the glucocorticoid treatment. Functional studies showed that the 96 h treatment did not affect the contractile response of guinea pig lung parenchymal strips to carbachol since the 50% concentration value (EC (50)) and the maximal contraction value (E(max)) were not significativ ely different from control values. These data show that glucocorticoid s control the expression of both muscarinic and beta-adrenergic recept ors in guinea pig lung but with different time courses and to a larger extent for muscarinic receptors. The glucocorticoid treatment did not modify the contractile response of lung strips to carbachol, confirmi ng the absence of effect on the affinity of muscarinic receptors and s uggesting that the receptor reserve exceed the increase of their densi ty by the steroid.