AJP - Lung Cellular and Molecular Physiology, Vol 266, Issue 6 698-L704, Copyright © 1994 by American Physiological Society
Alpha-adrenergic and muscarinic cholinergic inhibition of ACh release in guinea pig trachea: role of neuronal K+ channels
D. G. Baker, H. F. Don and J. K. Brown
Pulmonary and Critical Care Medicine Section, Veterans Affairs Medical Center, San Francisco 94121.
Our goals were to establish that an alpha 2-adrenergic agonist (clonidine)
inhibits ACh release from airway nerve endings and to test effects of
iberiotoxin (IBTX), an inhibitor of fast-conductance, Ca(2+)-activated K+
channels on alpha 2-adrenergic and muscarinic attenuation of ACh release.
Guinea pig tracheas were mounted between electrodes in buffer containing
indomethacin and neostigmine, and high-performance liquid chromatography
with electrochemical detection was used to measure ACh release during
electrical field stimulation. Clonidine inhibited ACh release in a
concentration-dependent fashion [maximum reduction: 48 +/- 3%; 50%
inhibitory constant (IC50): 0.1 microM], and idazoxan, alpha 2-adrenergic
antagonist, reversed the effect. However, IBTX failed to alter
clonidine-induced attenuation of ACh release. In contrast, IBTX did cause
an increase in tracheal tension. In addition, IBTX failed to reverse any of
the potent autoinhibitory effects of endogenous ACh. Our results confirm
the presence of inhibitory alpha 2-adrenergic receptors. However,
activation of IBTX-sensitive K+ channels does not appear necessary for
either alpha 2-adrenergic or muscarinic cholinergic inhibition of ACh
release.
