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Lipoxin A4 inhibits cholinergic neurotransmission through nitric oxide generation in the rabbit trachea
J Tamaoki1, E Tagaya, I Yamawaki
1First Department of Medicine, Tokyo Women's Medical College, Japan.
Abstract:
The effect of lipoxin A4 and lipoxin B4 on cholinergic neurotransmission in rabbit tracheal segments was studied under isometric conditions in vitro. Lipoxin A4 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 (ES50) increased from 8.1 +/- 0.8 to 25.7 +/- 1.9 Hz (P < 0.001), whereas lipoxin B4 had no effect. In contrast, lipoxin A4 did not alter the contractile responses to acetylcholine. Pretreatment of tissues with NG-nitro-L-arginine methylester inhibited the effect of lipoxin A4 on electrical field stimulation, but NG-nitro-D-arginine methylester did not. This inhibition by NG-nitro-L-arginine methylester was reversed by L-arginine but not by D-arginine. These results suggest that lipoxin A4 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.
Insights
Lipoxin A4 reduces airway smooth muscle contraction by inhibiting acetylcholine release, likely via nitric oxide. Lipoxin B4 showed no effect on this cholinergic neurotransmission.
Area of Science:
- Pharmacology
- Neuroscience
- Respiratory Medicine
Background:
- Cholinergic neurotransmission regulates airway smooth muscle tone.
- Lipoxins are inflammatory mediators with diverse biological effects.
Purpose of the Study:
- To investigate the effects of lipoxin A4 (LXA4) and lipoxin B4 (LXB4) on cholinergic neurotransmission in rabbit tracheal smooth muscle.
- To elucidate the potential mechanisms underlying LXA4's actions.
Main Methods:
- Isometric tension recordings in isolated rabbit tracheal segments.
- Electrical field stimulation (EFS) to assess cholinergic nerve-mediated contractions.
- Dose-response curves to acetylcholine (ACh).
- Pharmacological inhibition using NG-nitro-L-arginine methylester (L-NAME) and NG-nitro-D-arginine methylester (D-NAME).
Main Results:
- LXA4 significantly attenuated contractile responses to EFS, increasing the half-maximal effective stimulus frequency (ES50).
- LXB4 had no significant effect on EFS-induced contractions.
- LXA4 did not alter responses to direct acetylcholine application.
- L-NAME, but not D-NAME, inhibited LXA4's effect on EFS, and this inhibition was reversed by L-arginine.
Conclusions:
- LXA4 prejunctionally inhibits vagal nerve-mediated airway smooth muscle contraction.
- This inhibition is likely mediated by reduced acetylcholine release.
- The mechanism involves the stimulation of nitric oxide (NO) generation.