Post-synaptic potentiation of vagal contractile responses by neurokinin A

Abstract

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 bilateral stimulation of the vagus nerves, in 26 mongrel dogs. The tracheal contractile response to 10(-7) mol NKA was 3.12 +/- 0.48 g/cm, 6.3 +/- 0.7%AChmax. Plasma histamine concentration was measured in the right atrium at the peak response following administration of NKA. Plasma histamine concentration was 3.33 +/- 2.05 ng/ml after 10(-7) mol NKA (vs. 1.82 +/- 0.54 ng/ml for control, P > 0.10). A frequency-response curve was generated by electrical stimulation of the caudal ends of cut cervical vagi over the range of frequencies 1-20 Hz (constant 30 V) at 15 s intervals 10 min before and 10 min after administration of 10(-8) mol NKA. Substantial augmentation of tracheal contractile responses to 10(-10)-10(-7) mol ia ACh was obtained 10 min after administration of NKA (P < 0.05). Significant potentiation of tracheal contraction 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.