D. Spina et Rg. Goldie, POLY-L-ARGININE-MEDIATED RELEASE OF ACETYLCHOLINE FROM PARASYMPATHETIC NERVES IN RAT AND GUINEA-PIG AIRWAYS, British Journal of Pharmacology, 112(3), 1994, pp. 895-900
1 The synthetic cationic polypeptide, poly-L-arginine (0.03-1 mg ml(-1
)) induced concentration-dependent contraction of guinea-pig and rat i
solated trachea. In guinea-pig isolated trachea, this response was att
enuated in the presence of the muscarinic cholinoceptor antagonist, at
ropine (0.1 mu M) and augmented by the acetylcholinesterase inhibitor,
ecothiophate (0.1 mu M). The neuronal sodium channel blocker, tetrodo
toxin (3 mu M) failed to alter the contractile response to poly-L-argi
nine and acetylcholine. 2 The contractile response to poly-L-arginine
in rat isolated trachea was inhibited in the presence of atropine (0.1
mu M) and the 5-hydroxytryptamine (5-HT) receptor antagonist, methyse
rgide (1 mu M). Treatment of rat tracheal preparations with capsaicin
(100 mu M) or tetrodotoxin (3 mu M) failed to alter the contractile re
sponse to poly-L-arginine. In contrast, ecothiophate (0.1 mu M) augmen
ted the contractile response to poly-L-arginine in rat isolated trache
a.3 Electrical held stimulation (5 Hz, 2 min) of epithelium-denuded gu
inea-pig tracheal preparations preloaded with [H-3]-choline resulted i
n a contractile response and the simultaneous efflux of radioactivity
into the superfusate. Both these responses were abolished in the prese
nce of tetrodotoxin (1.5 mu M). Poly-L-arginine (1 mg ml(-1)) also inc
reased the efflux of total radioactivity from epithelium-denuded guine
a-pig isolated tracheal preparations preloaded with [H-3]-choline, but
this response was tetrodotoxin-insensitive, The negatively charged po
lyanion, heparin (1 mg ml(-1)) failed to increase significantly the ef
flux of radioactivity from epithelium-denuded preparations. 4 In concl
usion, the synthetic cationic polypeptide, poly-L-arginine, caused con
traction of guinea-pig isolated tracheal preparations via the release
of acetylcholine from parasympathetic nerves. Similarly, poly-L-argini
ne-induced contraction of rat isolated trachea is secondary to the rel
ease of acetylcholine from parasympathetic nerves and/or the release o
f mast cell-derived 5-HT.