INCREASED ACETYLCHOLINE-RELEASE IN TRACHEAS FROM ALLERGEN-EXPOSED IGE-IMMUNE MICE

Increased release of acetylcholine (ACh) from airway parasympathetic n erve endings is one mechanism that may contribute to increases in airw ay responsiveness in immunoglobulin E (IgE)-immune allergen-exposed an imals. We measured ACh released from murine tracheas following electri cal field stimulation in vitro. BALB/c mice were immunized by exposure to an aerosol of 1% ovalbumin in sterile phosphate-buffered saline fo r 20 min/day for 10 days. At this time, levels of ovalbumin-specific I gE were proportionately higher than oval-bumin-specific IgG. As a cont rol, nonimmune mice were similarly exposed to phosphate-buffered salin e alone. Forty-eight hours after the last aerosol, tracheas were remov ed for assessment of either the contractile responses to electrical fi eld stimulation and a cholinergic agonist (methacholine or ACh) or rel ease of ACh produced by electrical field stimulation. ACh in the bath was measured using high-performance liquid chromatography with electro chemical detection. The stimulation frequencies causing one-half the m aximal contractile response to electrical field stimulation were 4.1 /- 0.2 and 2.8 +/- 0.2 Hz (P = 0.0001) for nonimmune and immune mice, respectively, whereas the molar concentrations of methacholine causing one-half of the maximal contractile response did not significantly di ffer. In addition, the dose-response curves of immune and nonimmune tr acheas to ACh were superimposable. A significant increase in ACh relea se was demonstrated at both 10 and 20 Hz in tracheas from immune mice. ACh release (pmol.g tissue(-1) min(-1)) from nonimmune and immune mur ine tracheas, respectively, were 140 +/- 8 and 205 +/- 22 (P = 0.013) at 10 Hz and 147 +/- 13 and 227 +/- 14 (P = 0.008) at 20 Hz, An antago nist of the Mt muscarinic autoreceptor (gallamine) and an agonist for this receptor (pilocarpine) were able to modulate ACh release from tra cheas from nonimmune but not immune mice. These results suggest repeat ed airway exposure to allergen associated with the development of an I gE-responsive state leads to altered neural control of airways with in creased release of ACh from neural terminals. This increase in ACh rel ease was associated with loss of function of the M(2) muscarinic autor eceptor in tracheas from immune animals.