Lipoxin A 4 inhibits cholinergic neurotransmission through nitric oxide generation in the rabbit trachea

Abstract

The effect of lipoxin A 4 and lipoxin B 4 on cholinergic neurotransmission in rabbit tracheal segments was studied under isometric conditions in vitro. Lipoxin A 4 attenuated the contractile responses to electrical field stimulation and caused a rightward shift of the frequency-response curves, so that the stimulus frequency required to produce a half-maximal effect (ES 50) increased from 8.1 ± 0.8 to 25.7 ± 1.9 Hz ( P < 0.001), whereas lipoxin B 4 had no effect. In contrast, lipoxin A 4 did not alte contractile responses to acetylcholine. Pretreatment of tissues with N G-nitro- l-arginine methylester inhibited the effect of lipoxin A 4 on electrical field stimulation, but N G-nitro- d-arginine methylester did not. This inhibition by N G-nitro- l-arginine methylester was reversed by l-arginine but not by d-arginine. These results suggest that lipoxin A 4 prejunctionally reduces the vagal nerve-mediated contraction of airway smooth muscle, probably by inhibiting the release of acetylcholine, and that this effect may be exerted through stimulation of nitric oxide generation.