Glucocorticoid modulation of muscarinic and beta-adrenergic receptors in guinea pig lung.
We investigated the effect of the in vivo treatment of guinea pigs with methylprednisolone, 10 mg/kg daily, on lung muscarinic and beta-adrenergic receptors. Receptor densities were assessed by saturation experiments 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 of 39.7% (P < 0.01) and 16.9% (P < 0.05) was observed for muscarinic and beta-adrenergic receptors, respectively. For muscarinic receptors, this increase reached 53.4% (P < 0.01) within 48 h and stayed at this level 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 (Kd) values of both ligands were not affected by 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 (EC50) and the maximal contraction value (Emax) were not significatively different from control values. These data show that glucocorticoids control the expression of both muscarinic and beta-adrenergic receptors 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, confirming the absence of effect on the affinity of muscarinic receptors and suggesting that the receptor reserve exceed the increase of their density by the steroid.
Scherrer
D
D
Laboratoire de Neuroimmunopharmacologie, INSERM U425, Faculté de Pharmacie, Université Louis Pasteur Strasburg, Illkirch, France.
Lach
E
E
Landry
Y
Y
Gies
J P
JP
D000704:Analysis of Variance; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D005938:Glucocorticoids / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D008775:Methylprednisolone / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000187:drug effects*
D005938:Glucocorticoids; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; D002217:Carbachol; D008775:Methylprednisolone