Tachykinin-dependent and -independent components of peristalsis in the guinea pig isolated distal colon

Background & Aims: In-the intestine, tachykinins regulate motility by parti cipating in neuromuscular and neuro-neuronal transmission. The aim of this study was to test the hypothesis that colonic propulsion is regulated by an interplay between tachykinergic and cholinergic transmission. Methods: Pro pulsion was elicited by intraluminal distention of a thin rubber balloon, w hich traveled from the oral to the anal end of guinea pig isolated distal c olon segments. The overall contribution of endogenous tachyhinins to coloni c propulsion was examined by blocking NK1, NK2, and NK3 receptors simultane ously. Results: NK2-receptor blockade by MEN 11420 inhibited propulsion, wh ereas blockade of NK1 by SR 140333 or of NK3 receptors by SR 142801 had min or effects on motility, Blockade of muscarinic or nicotinic receptors by hy oscine or hexamethonium decelerated peristalsis up to propulsion arrest. In the presence of partial muscarinic receptor blockade, the NK1-receptor ant agonist SR 140333 and the NK2-receptor antagonist MEN 11420 markedly inhibi ted propulsion. Propulsion was also inhibited by the NK3-receptor antagonis t SR 142801 in the presence of partial nicotinic receptor blockade. The sim ultaneous administration of the 3 tachykinin antagonists inhibited propulsi on by 50%. Conclusions: This study demonstrates the existence of an interpl ay between tachykinergic and cholinergic pathways during peristalsis and th e importance of endogenous tachykinins acting at multiple receptor sites in the control of colonic propulsion.