POLY-L-ARGININE-MEDIATED RELEASE OF ACETYLCHOLINE FROM PARASYMPATHETIC NERVES IN RAT AND GUINEA-PIG AIRWAYS

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.