Glucocorticoid treatment increases inhibitory M-2 muscarinic receptor expression and function in the airways

M-2 muscarinic receptors on parasympathetic nerve endings inhibit acetylcho line release in the airways. In this study, the effects of dexamethasone on M-2 receptors in vivo and in primary cultures of airway parasympathetic ne urons were tested. Treating guinea pigs with dexamethasone (0.1 mg/kg, dail y for 2 d) substantially increased inhibitory M-2 muscarinic receptor funct ion, decreasing airway responsiveness to electrical stimulation of the vagi , At the same time, dexamethasone decreased the response to acetylcholine b ut not to methacholine, suggesting that cholinesterase activity was increas ed. When both cholinesterase and M-2 receptors were blocked (using physosti gmine 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 u sing atropine (10(-5) M) increased acetylcholine release. After the M-2 rec eptors were blocked there was no difference in acetylcholine release betwee n control and dexamethasone-treated cultures. M-2 receptor gene expression was increased by more than fivefold in dexamethasone-treated cultures. Immu nostaining of dexamethasone-treated neurons demonstrated more intense stain ing, Thus, decreased vagally mediated reflex bronchoconstriction after gluc ocorticoid treatment may be the result on increased M-2 receptor expression and function as well as increased degradation of acetylcholine by cholines terase.