Glucocorticoid treatment increases inhibitory m(2) muscarinic receptor expression and function in the airways

Am J Respir Cell Mol Biol. 2001 Apr;24(4):485-91. doi: 10.1165/ajrcmb.24.4.4379.


M(2) muscarinic receptors on parasympathetic nerve endings inhibit acetylcholine release in the airways. In this study, the effects of dexamethasone on M(2) 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 M(2) 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 M(2) 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 M(2) receptors using atropine (10(-5) M) increased acetylcholine release. After the M(2) receptors were blocked there was no difference in acetylcholine release between control and dexamethasone-treated cultures. M(2) 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 M(2) receptor expression and function as well as increased degradation of acetylcholine by cholinesterase.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcholine / metabolism
  • Acetylcholine / pharmacology
  • Animals
  • Atropine / pharmacology
  • Bronchoconstriction / drug effects
  • Bronchoconstriction / physiology
  • Cells, Cultured
  • Cholinergic Agents / metabolism
  • Cholinergic Agents / pharmacology
  • Cholinesterase Inhibitors / pharmacology
  • Dexamethasone / pharmacology*
  • Electric Stimulation
  • Gallamine Triethiodide / pharmacology
  • Glucocorticoids / pharmacology*
  • Guinea Pigs
  • Injections, Intravenous
  • Lung / innervation*
  • Methacholine Chloride / pharmacology
  • Muscarinic Agonists / pharmacology
  • Muscarinic Antagonists / pharmacology
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Nicotinic Antagonists / pharmacology
  • Parasympathetic Nervous System / cytology
  • Physostigmine / pharmacology
  • Receptor, Muscarinic M2
  • Receptors, Muscarinic / analysis
  • Receptors, Muscarinic / biosynthesis*
  • Vagus Nerve / cytology
  • Vagus Nerve / physiology


  • Cholinergic Agents
  • Cholinesterase Inhibitors
  • Glucocorticoids
  • Muscarinic Agonists
  • Muscarinic Antagonists
  • Nicotinic Antagonists
  • Receptor, Muscarinic M2
  • Receptors, Muscarinic
  • Methacholine Chloride
  • Atropine
  • Dexamethasone
  • Physostigmine
  • Acetylcholine
  • Gallamine Triethiodide