Presynaptic alpha-2 receptors inhibit norepinephrine release in tracheal smooth muscle.

The presence of inhibitory presynaptic alpha-2 adrenergic receptors and their ability to modulate nerve-mediated relaxation responses was examined in strips of canine tracheal smooth muscle (TSM). TSM strips were incubated with 3H-labelled norepinephrine (NE), rinsed, and mounted in superfusion chambers for electrical stimulation (ES) of the intramural adrenergic neurons. Yohimbine, an alpha-2 receptor antagonist, increased the release of [3H]NE into the superfusate during ES and decreased the amount of [3H]NE remaining in TSM strips after ES, indicating the presence of presynaptic alpha-2 receptors. Whether these alpha-2 receptors were functional in atropine-treated TSM was determined by comparing the inhibitory effect of ES on TSM contractions induced by histamine in the absence and presence of yohimbine. Relaxation of TSM strips at stimulus frequencies of 1-20 Hz was significantly greater in the presence of yohimbine. Moreover, the stimulus frequency required to produce a 50% relaxation, was 5.1 +/- 0.9 Hz in control strips, but only 2.1 +/- 0.4 in TSM strips pretreated with yohimbine. We conclude that presynaptic alpha-2 receptors serve a functional role in regulating NE release in canine TSM.