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Am. J. Respir. Cell Mol. Biol., Volume 24, Number 4, April, 2001 485-491

Glucocorticoid Treatment Increases Inhibitory M2 Muscarinic Receptor Expression and Function in the Airways

David B. Jacoby, Bethany L. Yost, Bharathy Kumaravel, Yee Chan-Li, Hui-Qing Xiao, Koichiro Kawashima, and Allison D. Fryer

Division of Pulmonary and Critical Care Medicine, School of Medicine, and Department of Environmental Health Sciences, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland; and Department of Pharmacology, Kyoritsu College of Pharmacy, Tokyo, Japan

M2 muscarinic receptors on parasympathetic nerve endings inhibit acetylcholine release in the airways. In this study, the effects of dexamethasone on M2 receptors in vivo and in primary cultures of airway parasympathetic neurons were tested. Treating guinea pigs with dexamethasone (0.1 mg/kg, daily for 2 d) substantially increased inhibitory M2 muscarinic receptor function, decreasing airway responsiveness to electrical stimulation of the vagi. At the same time, dexamethasone decreased the response to acetylcholine but not to methacholine, suggesting that cholinesterase activity was increased. When both cholinesterase and M2 receptors were blocked (using physostigmine and gallamine, respectively) vagally induced bronchoconstriction was increased to control values. In primary cultures of airway parasympathetic neurons, dexamethasone significantly decreased the release of acetylcholine in response to electrical stimulation. Blocking inhibitory M2 receptors using atropine (10-5 M) increased acetylcholine release. After the M2 receptors were blocked there was no difference in acetylcholine release between control and dexamethasone-treated cultures. M2 receptor gene expression was increased by more than fivefold in dexamethasone-treated cultures. Immunostaining of dexamethasone-treated neurons demonstrated more intense staining. Thus, decreased vagally mediated reflex bronchoconstriction after glucocorticoid treatment may be the result on increased M2 receptor expression and function as well as increased degradation of acetylcholine by cholinesterase.

Abbreviations: cellular RNA, cRNA; messenger RNA, mRNA; pulmonary inflation pressure, Ppi; reverse transcriptase/polymerase chain reaction, RT-PCR; standard error, SE.




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