Contribution of NK 3 tachykinin receptors to propulsion in the rabbit isolated distal colon[Note 1. Preliminary data emerging from this study have been communicated ...]

The role of NK 3 receptors in rabbit colonic propulsion has been investigated in vitro with the selective agonist, senktide, and two selective antagonists, SR142801 and SB222200. Peristalsis was elicited by distending a rubber balloon with 0.3 and 1.0 mL of water leading to a velocity of 2.2 and 2.8 mm s −1 , respectively. At concentrations of 1 n M , senktide inhibited propulsion evoked by both distensions (range 25–40%), whereas at 6 and 60 nmol L −1 facilitated ‘submaximal’ propulsion by 30%. In the presence of Nω‐nitro‐ L ‐arginine ( L ‐NNA, 200 μmol L −1 ), which per se caused a slight prokinetic effect, 1 nmol L −1 senktide markedly accelerated propulsion (range 35–50%). Hexamethonium (200 μmol L −1 ) had minor effects on propulsion. In its presence, 60 nmol L −1 senktide significantly inhibited propulsion induced by both stimuli (range 20–50%). SR142801 (0.3, 3 nmol L −1 ) and SB222200 (30, 300 nmol L −1 ) facilitated ‘submaximal’ propulsion (range 20–40%). Conversely, higher antagonist concentrations (SR142801: 30, 300 n M ; SB222200: 1, 10 μmol L −1 ) inhibited propulsion to both distensions by 20%. A combination of SR142801 (300 nmol L −1 ) plus hexamethonium (200 μmol L −1 ) induced an approximately four‐fold greater inhibition of propulsion than that induced by SR142801 alone. In conclusion, in the rabbit‐isolated distal colon, a subset of NK 3 receptors located on descending pathways mediates an inhibitory effect on propulsion by activating a NO‐dependent mechanism. Another subset of NK 3 receptors, located on ascen ding pathways mediates a facilitative effect involving a synergistic interaction with cholinergic nicotinic receptors.