Role of tachykinin receptors in the modulation of colonic peristaltic activity in mice

Tachykinins are important mediators of neuroneuronal and neuromuscular transmission in the gastrointestinal tract, however their contribution to colonic peristalsis in mice remains unclear. Therefore, our aim was to characterise the functional role of tachykinins in mediating peristalsis by evaluating the effect of selective tachykinin NM1, NK2 and NK3 receptor agonists and antagonists on in vitro colonic peristaltic activity in mice. Using a modified Trendelenburg set-up, gradual distension of proximal and distal colonic segments evoked rhythmic, aborally migrating contractions. Peristaltic activity was assessed by quantifying the amplitude and interval of the corresponding pressure waves. Stimulation of NK1 receptors showed regional differences as both the pressure amplitude and interval were enhanced in the distal colon without affecting peristalsis proximally. Blockade of NK1 receptors reduced the peristaltic pressure amplitude in the proximal and distal colon while the interval was not significantly altered. NK2 receptor stimulation resulted in a modest enhancement of the amplitude in proximal and distal segments and a slightly prolonged interval distally. Blockade of NK2 receptors reduced the peristaltic pressure amplitude and interval in the distal colon. NK3 receptor stimulation significantly augmented the amplitude in both segments and prolonged the interval distally. However, NK3 receptor blockade had no effect on peristaltic activity. In conclusion, tachykinins contribute to colonic peristalsis in mice by acting mainly on NK1 and NK2 receptors and their effects show a proximal-to-distal gradient. NK3 receptors might play a role in conditions of excess tachykinin release but appear not to be involved under the conditions of the present study. (C) 2011 Elsevier B.V. All rights reserved.