ALPHA-ADRENERGIC AND MUSCARINIC CHOLINERGIC INHIBITION OF ACH RELEASEIN GUINEA-PIG TRACHEA - ROLE OF NEURONAL K+ CHANNELS

Our goals were to establish that an alpha(2)-adrenergic agonist (cloni dine) inhibits ACh release from airway nerve endings and to test effec ts of iberiotoxin (IBTX), an inhibitor of fast-conductance, Ca2+-activ ated K+ channels, on alpha(2)-adrenergic and muscarinic attenuation of ACh release. Guinea pig tracheas were mounted between electrodes in b uffer containing indomethacin and neostigmine, and high-performance li quid 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: 4 8 +/- 3%; 50% inhibitory constant (IC50): 0.1 mu M], and idazoxan, alp ha(2)-adrenergic antagonist, reversed the effect. However, IBTX failed to alter clonidine-induced attenuation of ACh release. In contrast, I BTX did cause an increase in tracheal tension. In addition, IBTX faile d to reverse any of the potent autoinhibitory effects of endogenous AC h. 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 choliner gic inhibition of ACh release.