EFFECT OF IMMUNE SENSITIZATION ON STIMULATED ACH RELEASE FROM TRACHEALIS MUSCLE IN-VITRO

We assessed the effect of immune sensitization on acetylcholine (ACh) release from parasympathetic nerve terminals in tracheal smooth muscle (TSM) strips from ragweed-sensitized (RWS) and sham-sensitized, litte rmate control (LMC) dogs. Strips of TSM were tethered to force transdu cers at optimal length in perfusion chambers containing [H-3]choline a nd a fixed volume of physiological perfusate. Tissues were equilibrate d for 1 h by electrical field stimulation (EFS) every 5 min to facilit ate uptake of label into parasympathetic nerves as ACh. Fresh perfusat e (containing 3 x 10(-8) M physostigmine) was collected at 5-min inter vals for 1 h, and a rate coefficient of [H-3]ACh release was determine d. Tissues were exposed to agonists in the seventh collection period, and the increase in label release (ratio change where less-than-or-equ al-to 1.00 = baseline) and force production were determined. Ragweed a ntigen challenge stimulated [H-3]ACh release and contraction in RWS bu t not LMC tissues. [H-3]ACh release was 1.93 +/- 0.22 x baseline in RW S vs. 0.92 +/- 0.02 in control tissues (P < 0.01); contraction was 31. 2 +/- 9.5% of that elicited by EFS (% EFS) in RWS vs. 0% EFS in LMC ti ssues (P < 0.01). Strips of TSM from RWS but not LMC dogs demonstrated concentration-dependent, augmented release of ACh caused by histamine . After 10(-4) M histamine, [H-3]ACh release in RWS was 1.94 +/- 0.37 x baseline vs. 1.05 +/- 0.06 for LMC tissues (P < 0.05); histamine als o caused greater contraction in RWS (106.5 +/- 5.9% EFS) vs. LMC (86.5 +/- 5.6% EFS; P < 0.05). We demonstrate augmented [H-3]ACh release st imulated by ragweed antigen and histamine from TSM from immune-sensiti zed (but not sham-sensitized) dogs. Our data suggest immune sensitizat ion facilitates release of neurotransmitter from postganglionic parasy mpathetic nerves in airway smooth muscle.