Potentiation of acetylcholine release from tracheal parasympathetic nerves by camp. Zhang, Xiang-Yang, N. Edward Robinson, and Feng-Xia Zhu. Departments of Large Animal Clinical Sciences and Physiology, Michigan State University, East Lansing, MI 48824
APStracts 2:0200L, 1995.
We tested the hypothesis that increasing intracellular levels of cAMP increase acetylcholine (ACh) release from airway parasympathetic nerves. Muscle strips from equine trachea were pre-incubated for 60 min with 10-7 M atropine, 10-6 M neostigmine, and 10-5 M guanethidine. The ACh release was evoked by electrical field stimulation (EFS, 20 V, 0.5 ms, 0.5 Hz) and measured by high -performance liquid chromatography with electrochemical detection. Agents known to increase cAMP, i.e., forskolin (10-6_10-4 M), 8-bromo cAMP (10-5_10-3 M), and 3-isobutyl-1-methylxanthine (IBMX: 10-5_10-3 M) facilitated EFS-induced ACh release in a concentration-dependent manner. Forskolin-induced augmentation of ACh release was potentiated by IBMX, but not mimicked by 1,9-dideoxyforskolin. To determine if the augmentation of ACh release induced by activation of [beta]2 -adrenoceptors is mediated via cAMP-dependent pathways, we also examined the additive effects of 8-bromo cAMP, forskolin, and IBMX with 10-6 M isoproterenol (ISO), the concentration that maximally augments ACh release. Neither forskolin nor 8-bromo cAMP potentiated the maximal augmentation produced by ISO, but inhibition of phosphodiesterase with IBMX (10-4 and 10-3 M) augmented the maximal effect of ISO. These observations indicate that neuronal cAMP is a physiological modulator of ACh release from airway parasympathetic nerves, and mediates ISO-induced augmentation of ACh release. Bronchodilators that increase cAMP may therefore paradoxically augment ACh release while relaxing smooth muscle. 

Received 16 May 1995; accepted in final form 19 October 1995.
APS Manuscript Number L151-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95