Lipoxin A4 inhibits cholinergic neurotransmission through nitric oxide generation in the rabbit trachea.
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.
Tamaoki
J
J
First Department of Medicine, Tokyo Women's Medical College, Japan.
Tagaya
E
E
Yamawaki
I
I
Konno
K
K
D000109:Acetylcholine / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D044045:Lipoxins; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000187:drug effects; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011817:Rabbits; D009435:Synaptic Transmission / Q000187:drug effects*; D014132:Trachea / Q000187:drug effects / Q000378:metabolism; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D006893:Hydroxyeicosatetraenoic Acids; D044045:Lipoxins; C040527:lipoxin A4; D009569:Nitric Oxide; C042651:lipoxin B4; D019001:Nitric Oxide Synthase; D015232:Dinoprostone; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester