Research for the mechanism of bronchinal hyperresponsiveness

点击翻译按钮获取中文摘要

We have studied the effect of neurokinin A (NKA) on tracheal smooth muscle (TSM) contraction caused by administration of acetylcholine (ACh) intra-arterially (ia) into the tracheal circulation, or a bilateral stimulation of the vagus nerves in 26 mongrel dogs. As a result, substantial augmentation of tracheal contractile responses to 10^<-10>-10^<-7> molia ACh was obtained 10 min after administration of NKA (p<0.05). Significant potentiation of tracheal contractiion to vagal stimulation for 10-20 Hz was also observed after administration of 10^<-8> mol NKA (p<0.05). We have demonstrated a substantial contractile effect of NKA on canine tracheal smooth muscle that is not related to histamine release from respiratory mast cells. We have also demonstrated that NKA causes augmentation of the parasympathetic tracheal contractile response induced by ia administration of ACh and efferent vagus nerve stimulation. These data suggest that potentiation of vagal contractile response by NKA is related to post-synaptic activation of the parasympathetic nerves.The effect of FK224 on isometric contraction of canine tracheal smooth muscle in situ was studied. Contraction was induced by administration of substance P,neurokinin A,and neurokinin B intra-arterially into the tracheal circulation in five mongrel dogs. FK224 inhibited substance P- and neurokinin A-induced contraction in a dose-dependent manner, but it did not inhibit neurokinin B-induced contraction significantly. These data suggest that FK224 is a sural antagonist of both neurokinin 1 andd neurokinin 2 receptors with a similar potency in in vivo experiments.