Poly‐l‐arginine‐mediated release of acetylcholine from parasympathetic nerves in rat and guinea‐pig airways

Abstract

1 The synthetic cationic polypeptide, poly-L-arginine (0.03-1 mg ml-') induced concentrationdependent contraction of guinea-pig and rat isolated trachea. In guinea-pig isolated trachea, this response was attenuated in the presence of the muscarinic cholinoceptor antagonist, atropine (0.1 gM) and augmented by the acetylcholinesterase inhibitor, ecothiophate (0.1 M). The neuronal sodium channel blocker, tetrodotoxin (3 .M) failed to alter the contractile response to poly-L-arginine and acetylcholine. 2 The contractile response to poly-L-arginine in rat isolated trachea was inhibited in the presence of atropine (0.1 ILM) and the 5-hydroxytryptamine (5-HT) receptor antagonist, methysergide (1 g.M). Treatment of rat tracheal preparations with capsaicin (1 00 M) or tetrodotoxin (3 gM) failed to alter the contractile response to poly-L-arginine. In contrast, ecothiophate (0.1 JLM) augmented the contractile response to poly-L-arginine in rat isolated trachea. 3 Electrical field stimulation (5 Hz, 2 min) of epithelium-denuded guinea-pig tracheal preparations preloaded with [3H]-choline resulted in a contractile response and the simultaneous efflux of radioactivity into the superfusate. Both these responses were abolished in the presence of tetrodotoxin (L.5 gM).Poly-L-arginine (1 mg ml-') also increased the efflux of total radioactivity from epithelium-denuded guinea-pig isolated tracheal preparations preloaded with [3H]-choline, but this response was tetrodotoxin-insensitive. The negatively charged polyanion, heparin (1 mg ml-') failed to increase significantly the efflux of radioactivity from epithelium-denuded preparations. 4 In conclusion, the synthetic cationic polypeptide, poly-L-arginine, caused contraction of guinea-pig isolated tracheal preparations via the release of acetylcholine from parasympathetic nerves. Similarly, poly-L-arginine-induced contraction of rat isolated trachea is secondary to the release of acetylcholine from parasympathetic nerves and/or the release of mast cell-derived 5-HT.

Distribution of Major Basic Protein on Human Airway following In Vitro Eosinophil Incubation

“…We [ 18 ] have previously shown that MBP directly elicits airway myocyte calcium mobilization. Others have shown that an indirect effect of MBP may be through an effect on epithelial-derived mediator release [ 32 – 34 ], increased epithelial permeability [ 35 ], cytotoxicity [ 36 ], or by inhibiting muscarinic M 2 receptors [ 16 ]. These conflicting results may be due to the manner in which purified MBP is applied to tissues and cells in culture.…”

The effect of allosteric antagonists in modulating muscarinic M2‐receptor function in guinea‐pig isolated trachea

“…We could not use higher concentrations of poly-L-arginine due to the ability of this synthetic polypeptide to contract airway smooth muscle (Spina & Goldie, 1994a). Indeed, we have demonstrated that the poly-L-arginine-induced contraction of guinea-pig isolated trachea is mediated via the release of acetylcholine from parasympathetic nerves (Spina & Goldie, 1994b).…”

LPS Cooperates with Poly-L-Arginine to Promote IL-6 and IL-8 Release via the JNK Signaling Pathway in NCI-H292 Cells

“…The role of eosinophils in asthma is a consequence of their abilities to secrete eosinophil granule proteins, including major basic protein (MBP), which is highly basic and cationically charged [9]. MBP released from activated eosinophils may generate AHR by either direct effects on airway myocytes or indirect effects [10] through the release of epithelial-derived mediators [11–13], resulting in increased epithelial permeability [14], cytotoxicity [15], or the inhibition of muscarinic M2 receptors [16]. The effects of MBP can be mimicked by PLA, a synthetic cationic polypeptide.…”